Viral Hepatitis Flashcards
(106 cards)
1
Q
How many deaths occur worldwide due to viral hepatitis and what is the WHO goal?
A
1.5 million deaths annually
WHO goal = eliminate viral hepatitis by 2030
2
Q
Which viral hepatitis is treatable, curable and preventable?
A
Treatable - HBV
Curable - HCV
Preventable - HAV, HBV
3
Q
What are non-infectious causes of hepatitis?
A
Toxins
Medication
Alcohol
Autoimmune
4
Q
Name non-viral infectious causes of hepatitis
A
Bacterial (TB, syphilis)
Protozoal (malaria, amoebiasis)
Cestodes (hydatid)
Trematodes (schistosomiasis)
5
Q
Name hepatotrophic viral infectious causes of hepatitis
A
HAV
HBV
HCV
HDV
HEV
6
Q
Name non-hepatotrophic viral infectious causes of hepatitis
A
Adenovirus
EBV
CMV
HSV
Yellow fever
Measles
Rubella
7
Q
Which hepatotrophic virus is DNA?
A
HBV
HAV, HCV, HDV, HEV are RNA
8
Q
Which hepatotrophic viruses are enteric?
A
HAV
HEV
9
Q
Which hepatotrophic viruses are parenteral?
A
HBV
HCV
HDV
10
Q
What are the clinical features of acute hepatitis?
A
- Asymptomatic
- Prodrome
- Illness
11
Q
What are the clinical features of acute hepatitis prodrome?
A
Fever
Headache
Malaise
Fatigue
Anorexia
N+V
Abdominal pain
12
Q
What are the clinical features of acute hepatitis illness?
A
Icterus (dark urine, pale stools, pruritis, jaundice)
Hepatomegaly
Extrahepatic (arthralgia, rash)
13
Q
Can you identify causative organism of acute hepatitis based on laboratory markers?
A
No - virus specific assay is required for diagnosis
14
Q
Which laboratory markers are altered in acute hepatitis?
A
ALT, AST, ALP
Bilirubin
PTT
Inflammatory markers
15
Q
What is the epidemiology of HAV?
A
1.4 million cases annually
Sporadic vs epidemic
- poor sanitation
- day care
- travellers
- homeless
16
Q
What is the transmission of HAV?
A
Feco-oral
17
Q
What is the incubation period of HAV?
A
1 month (15-50d)
18
Q
What do HAV symptoms depend on?
A
Age
Children <6y 70% asymptomatic
Adults 70% symptomatic
19
Q
Discuss the outcomes of HAV infection
A
Usually mild and self-limiting (2-6m)
No chronicity
No re-infection
Complications increased with age
20
Q
Name complications of HAV
A
- Fulminant hepatitis
- Cholestatic jaundice
- Relapsing hepatitis
21
Q
Discuss the features of fulminant hepatitis in HAV
A
Encephalopathy
Coagulopathy
High fatality
22
Q
Discuss the features of cholestatic jaundice in HAV
A
Persistent severe jaundice and pruritic for up to 3m that resolves spontaneously
23
Q
Discuss the features of relapsing hepatitis in HAV
A
Biochemical and clinical relapse after initial recovery
Virus sheds in stool
Full recovery within 1y
Does not cause carrier state
24
Q
Discuss serology concerning HAV
A
Anti-HAV IgM - active/recent infection
Anti-HAV IgG - persists for life (immunisation)
25
How long can anti-HAV IgM persist?
Up to 6 months
26
Which assay results confirm HAV infection?
Symptoms with positive anti-HAV IgM
27
Discuss prevention of HAV
1. General
- sanitation
- proper food cooking
- hand hygiene
- infection control
- food safety inspections
2. Specific
- HNIG
- vaccine
28
What is HNIG?
Pooled human normal immunoglobulin
29
When can HNIG be used?
1. PrEP
2. PEP
3. High risk (immunocompromised)
30
When can HAV vaccine be used?
1. PrEP 2 weeks before travel and booster at 6 months
2. PEP within 14 days of exposure
31
Which HAV PrEP is preferred?
Vaccine > HNIG
32
Discuss HAV vaccination
Targeted
- risk of exposure (travellers, occupational)
- risk of complications (immunocompromised, liver disease)
Universal
- childhood vaccination could eradicate HAV (humans are the only host)
33
Discuss treatment of HAV
Supportive
Avoid hepatotoxic drugs
Restrict activity until LFTs normalise
Liver transplant if fulminant hepatitis
34
Discuss the epidemiology of HBV
250 million carriers worldwide
Age inversely related to chronicity
SA prevalence is 7% with genotype A
35
What is important about the HBV genotype found in SA?
Genotype A
- higher risk of chronicity
- higher risk of HCC
36
Discuss transmission of HBV
Horizontal
- blood exposure
- sexual exposure
- percutaneous
Vertical
- MTCT
37
Which factors increase risk for MTCT of HBV?
E antigen positive
High viral load
38
Which factors increase risk for percutaneous transmission of HBV?
E antigen positive
39
What is the incubation period of HBV?
3 months (1-6m)
40
Discuss the clinical features of acute HBV
1. Asymptomatic
2. Prodromal
3. Pre-icteric
4. Icteric
5. Post-icteric
Symptoms resolve within 3 months but fatigue may persist
41
What is the definition of chronic HBV?
Persistence of HBsAg >6m
Often asymptomatic or non-specific symptoms
42
Discuss the risk of chronicity in HBV
Perinatal risk 90-95%
>20y risk <5%
43
Discuss the outcomes of chronic HBV
1. Spontaneous surface antigen clearance (sAg negative and HBV DNA positive - occult infection)
2. Inactive chronic carrier state (sAg positive)
3. Disease progression (cirrhosis, decompensation, HCC)
44
What makes HBV challenging to cure?
Covalently closed circular HBV DNA (cccDNA) is found within the nucleus
Persistent, stable "mini-chromosome" from which virus copies are made
Nucleoside analogues do not eliminate cccDNA
45
What is the first serological marker in HBV?
HBsAg
46
Which HBV serological marker indicates infection?
HBsAg
>6m = chronic infection
47
Which HBV serological marker indicates active replication?
eAg (absent in some mutant viruses)
48
What does anti-HBc IgG indicate?
Past infection
49
What does anti-HBc IgM indicate?
Acute infection or reactivation
50
What does anti-HBs indicate?
Immunity (past infection or vaccination)
51
What is HBV DNA/VL useful for?
Identifying occult infection where HBsAg negative
Disease progression monitoring
Transmission risk
Treatment monitoring
52
Discuss the treatment of acute HBV infection
Supportive
Prevent further transmission
Can consider nucleoside analogues in specific indications (severe disease)
53
Which treatment is contraindicate in acute HBV infection?
Peg-interferon
54
What is the pre-treatment assessment of HBV?
Age
Disease severity
Comorbidities
Serological profile
VL, genotype
HCC screening (U/S, AFP, fibrosis markers, biopsy, endoscopy)
55
Discuss treatment options for HBV
Pegylated interferon
TAF
TDF
Entecavir
Lamivudine
56
Discuss the advantages of interferon treatment of HBV
Finite duration (48w)
No drug resistance
57
Discuss the disadvantages of interferon treatment of HBV
Injection
S/E
Contraindications (pregnancy, decompensated cirrhosis)
58
Discuss the advantages of nucleoside analogue treatment of HBV
Oral
Potent
Well-tolerated
Multiple options
59
Discuss the disadvantages of nucleoside analogue treatment of HBV
Long term treatment (>5y)
Drug resistance
60
When can HBV treatment be stopped in certain patients?
Undetectable HBsAg and HBeAg
HBsAb and HBeAb
Undetectable HBV DNA
Normal LFTs
61
Which nucleoside analogue is suitable for HBV treatment in children 2-11y?
Entecavir
62
Discuss strategies for HBV prevention
Infection control
Blood product screening
Donor organ screening
Needle exchange programs
Counselling of infected persons
Vaccination (PrEP and PEP)
62
Which factors indicate need for HBV treatment?
Cirrhosis (APRI >2)
HBV DNA > 20 000
63
Which patients should be targeted for HBV PrEP vaccination?
HCWs
Household contacts of HBV patients
Dialysis, transplant, frequent transfusion recipients
Comorbidities (HIV, chronic liver disease)
64
Which patients should be considered for HBV PEP vaccination?
Occupational exposure
Newborns of infected mothers
Sexual assault
65
If patient is exposed to HBV but unvaccinated/non-immune, what should be added?
Hepatitis B immunoglobulin
66
Discuss the epidemiology of HCV
70 million worldwide
1% low risk groups
>10% high risk groups
67
Discuss HCV transmission
1. Parenteral
2. Sexual
3. Vertical
68
What is the incubation period of HCV?
2 months (2w-6m)
69
Discuss the clinical features of HCV
1. Usually asymptomatic
2. Chronic - symptomatic when cirrhosis, HCC
70
Discuss the natural history of HCV infection
15% resolve
85% chronic
20 year progression
20% of chronic become cirrhotic
6%/y develop ESLD
4%/y develop HCC
3-4%/y require transplant or die
71
Name extra hepatic manifestations of HCV
Autoimmune (Sjogren's)
Porphyria cutanea tarda
Lymphoproliferative disease
Insulin resistance
72
What does HCV Ab negative HCV RNA negative indicate?
No chronic infection (acute possible if very recent infection)
73
What does HCV Ab negative HCV RNA positive indicate?
Acute infection
74
What does HCV Ab positive HCV RNA positive indicate?
Acute OR chronic infection
75
What does HCV Ab positive HCV RNA negative indicate?
Previous HCV infection
Confirm with repeat test in 12w
76
Discuss HCV treatment
Antivirals to all chronic patients
If acute HCV, may defer and recheck HCV RNA due to spontaneous resolution possibility
77
When do we say HCV is cured?
Undetectable HCV RNA >12w post treatment completion
78
What should you monitor regularly with direct acting antivirals?
FBC
LFT
Creat
INR
HCV RNA VL
79
Name the 3 targets of direct acting antivirals (DAAs) in HCV treatment
1. NS3/4A protease
2. NS5A
3. NS5B polymerase
80
Name examples of NS3/4A protease DAAs
Simeprevir
Grazoprevir
Voxilaprevir
Glecaprevir
81
Name examples of NS5A DAAs
Daclastavir
Ledipasvir
Elbasvir
Velpatasir
Pibrentasvir
82
Name examples of NS5B polymerase DAAs
Sofosbuvir
Dasabuvir
83
Name HCV treatment options in patients >18y without cirrhosis
Sofos/velpa 12w
Sofos/dacla 12w
Gleca/pibre 8w
84
Name HCV treatment options in patients <18y with compensated cirrhosis
Sofos/velpa 12w
Gleca/pibre 12w
Sofos/dacla 24w
85
Name HCV treatment options in patients 12-17y
Genotypes
1, 4, 5, 6 - sofos/ledi 12w
2 - sofos/riba 12w
3 - sofos/riba 24w
86
Which family does HAV belong to?
Hepatovirus
87
Which family does HBV belong to?
Hepadnavirus
88
Which family does HCV belong to?
Hepacivirus
89
Which family does HDV belong to?
Deltavirus
90
What are the features of acute hepatitis on pathology?
1. Hepatocellular damage (minor cell swelling to apoptosis)
2. Councilman bodies
3. Varying degrees of necrosis
4. Cholestasis
5. Mild siderosis
6. Mild steatosis
7. Portal tracts infiltrated with mixed inflammatory cells
8. Bile duct proliferation
91
What are 'councilman bodies'?
Apoptotic bodies
92
What are the features of chronic hepatitis on pathology?
Inflammatory infiltrate
Interface hepatitis
Bridging necrosis -> fibrosis -> cirrhosis
93
What is specific about the inflammatory infiltrate in HCV?
Lymphoid aggregates
94
Discuss the features of hepatic steatosis
Moderate alcohol intake - microvesicular steatosis
Chronic alcohol intake - macrovesicular steatosis
Fatty change is initially centrilobular -> pan lobular in severe cases
Minimal fibrosis
Continued alcohol consumption -> fibrous tissue development around central veins
95
Until what point is fatty change in hepatic steatosis reversible?
Until fibrosis appears
96
Discuss the characteristics of alcoholic hepatitis
Hepatocyte swelling
Spotty necrosis
Neutrophil reaction (lobules)
Mallory bodies
Sinusoidal and perivenular fibrosis
97
What are mallory bodies?
Eosinophilic inclusions in hepatocyte cytoplasm
98
Can alcoholic cirrhosis develop without evidence of steatosis or alcoholic hepatitis?
Yes
99
What can liver cysts mimic?
Malignant tumours
100
What are 3 main types of liver cysts?
1. Simple cysts
2. Hydatid cysts (echinococcus granulosus)
3. Choledochal cysts (congenital, intra vs extra hepatic)
101
What is the most common visceral malignant tumour?
Hepatocellular carcinoma
102
Discuss the epidemiology of hepatocellular carcinoma
M>F
20-40yo
Strongly linked to HBV
Vertical transmission 200x risk for HCC
<50% have cirrhosis
103
What are other aetiologies of HCC?
Aflatoxins (aspergillus flavus)
Vinyl chloride
Thorotrast
104
Discuss the pathology features of HCC
Usually solitary
Multifocal in cirrhosis
Hemorrhagic, necrotic masses
Bile stained
Rapidly growing
May infiltrate large veins eg vena cava
Seldom metastasises but can go to. lung
Death within 10m of diagnosis
Incr AFP in 75% of patients
105
