Hepatitis (BHIVA 2013) Flashcards
1
Q
Why should all PLW HIV be screened for HEPATITIS A?
A
Vaccine-preventable disease
2
Q
What complications occur in people with persistent HEPATITIS B?
A
chronic progressive liver disease hepatocellular carcinoma (HCC)
3
Q
How many GENOTYPES of HEPATITIS B are there?
A
TEN (10)
4
Q
What value does HEPATITIS B genotype testing offer?
A
helps predict outcome with PEGYLATED INTERFERON
5
Q
What is the definition of ‘chronic persistence’ of HEPATITIS B?
A
HB surface antigen DETECTABLE
>6 months
6
Q
What proportion of PLW HIV have detectable HBsAg?
A
7%
7
Q
What factors were associated with detectable HBsAg in PLW HIV?
A
Black person
IDU
MSM
8
Q
What might explain an isolated HBcAb in the absence of HBsAg or evidence of immunity in PLW HIV?
A
FALSE positive or loss of HBsAb due to IMMUNE DYSFUNCTION or loss of HBsAg before HBsAb (less likely)
9
Q
What proportion of people with isolated HBcAb will eventually develop HBsAb over time?
A
20-40%
10
Q
What proportion of people with isolated HBcAb will develop SURFACE antigen?
A
2-4%
11
Q
In a person with previous isolated HBcAb who develops HBsAg, what does this indicate?
A
REACTIVATION
or
NEW infection
12
Q
Which group of people are at highest risk of HEPATITIS C?
A
IDU
13
Q
What is the prevalence of HEPATITIS C in PLW HIV?
A
9%
14
Q
What risk factors increase a PLW HIV of acquiring HEPATITIS C?
A
MSM \+ multiple partners STI insertive anal sex douches/enemas
15
Q
What is the re-infection rate for HEPATITIS C in PLW HIV?
A
8-25%
UK vs Dutch cohort
16
Q
At what clinical stage is PEG-IFN and ribavirin more successful in treatment for HEPATITIS C?
A
ACUTE infection
note - old treatment
17
Q
What impact does HIV infection have on HEPATITIS C seroconversion?
A
DELAYS
18
Q
What factors are associated with DELAYED seroconversion of HEPATITIS C in PLW HIV?
A
low ALT
low CD4
19
Q
What molecular aspects of HEPATITIS C virus are associated SPONTANEOUS CLEARANCE?
A
Single nucleotide polymorphisms in IL28B locus on Chromosome 19
20
Q
What was the past ‘gold standard’ for staging and grading liver disease?
A
Liver BIOPSY
21
Q
What is the modern day choice of investigation to assess for liver fibrosis?
A
Hepatic Transient Elastography (TE)
Fibroscan
22
Q
At what level of kPa is cirrhosis diagnosed on fibroscan in HEPATITIS B?
A
> 11kPa
23
Q
At what level of kPa is cirrhosis diagnosed on fibroscan in HEPATITIS C?
A
> 14.5kPa
24
Q
What is the limitation of hepatic transient elastography (ie Fibroscan)?
A
less accurately differentiates between lower levels of fibrosis
25
If there is uncertainty of level of fibrosis on hepatic transient elastography what alternative investigation can be performed?
Liver BIOPSY
26
What is the vaccination schedule for HEPATITIS B in PLW HIV?
DOUBLE dose
40 microgram
0, 1, 2 and 6 months
27
When can an accelerated hepatitis B vaccination schedule be used in PLW HIV?
need for RAPID completion
AND
CD4 >500 cells
28
When should HBsAb levels be checked following hepatitis B vaccination?
4-8 weeks after last dose
| check - is this old guidance
29
If HBsAB titre is less than 10IU/L after vaccination course, what is the recommended action?
RE-VACCINATE 3 doses
40microgram
MONTHLY
30
If HBsAB titre is between 10IU/L to 100IU/L after vaccination course, what is the recommended action?
ONE further vaccine
40 microgram
re-check HBsAb 4-8 weeks
31
When is a BOOSTER dose of vaccine indicated for HEPATITIS B?
HBsAB <10IU/L
32
What is the dose of hepatitis B booster dose?
40microgram
33
How many weeks post vaccination is the presence or not of HBsAb predictive of durability of immunity?
28 weeks
34
What is the incidence of ART related severe HEPATOTOXICITY?
10%
35
What increases the risk of ART related hepatotoxicity?
Hepatitis + HIV co-infection
36
What modifiable lifestyle factors in particular may increase the risk of ART related hepatotoxicity?
ALCOHOL
| COCAINE
37
Which ART can induce a hypersensitivity reaction which includes hepatotoxicity?
```
NEVIRAPINE
DARUNAVIR
FOSAMPRENAVIR
DIDANOSINE
TIPRANAVIR
```
38
What liver condition is didanosine specifically associated with?
Non-cirrhotic portal hypertension
39
Which ART may reduce the efficacy of PEG-IFN/RBV treatment for HCV?
ABACAVIR
40
What dose adjustment is required for RIBAVIRIN if a person is taking ABACAVIR?
Increase ribavirin
41
Why might a person have high HBV DNA but surface antigen negative?
Drug selective pressure
Often on lamivudine
mutations in the surface gene
42
What impact does HIV have on hepatitis B outcomes [name 4 things]?
1) more likely to progress to chronic HBV
2) Lower clearance of eAg
3) Higher viral load than HBV alone
4) more rapid progression to cirrhosis/HCC
43
Presence of HBsAg after what time period is diagnostic of chronic infection?
6 months
44
In what circumstance might HBcAb IgG not develop in HBV + HIV co-infection?
Advanced immunosuppression
45
Hepatitis B infection - describe IMMUNE TOLERANT stage.
```
HBsAg POSITIVE
HBeAg POSITIVE
HBV DNA HIGH
ALT/AST NORMAL
BIOPSY - little or no fibrosis
```
46
In what population is HBV immune tolerant stage most likely to occur?
those infected in EARLY CHILDHOOD or VERTICAL transmission
47
Hepatitis B infection - describe IMMUNE ACTIVE stage.
```
HBsAg POSITIVE
HBeAg POSITIVE
HBV DNA HIGH
ALT/AST RAISED
BIOPSY - inflammation/fibrosis
```
48
In what population is HBV immune active stage most likely to occur?
those infection in OLDER CHILDHOOD or ADULT
49
Hepatitis B infection - describe IMMUNE CONTROL stage.
```
Inactive
HBsAg POSITIVE
HBeAg NEGATIVE
HBV DNA VERY LOW
ALT/AST NORMAL
BIOPSY - not required
```
50
Hepatitis B infection - describe eAg NEGATIVE CHRONIC ACTIVE stage.
```
HBsAg POSITIVE
HBeAg NEGATIVE
HBV DNA FLUCTUATING
ALT/AST FLUCTUATING
BIOPSY - inflammation/fibrosis
```
51
What is the GENETIC BARRIER to resistance for lamivudine, emtricitibine, telbivudine for HBV?
LOW
52
What is the GENETIC BARRIER to resistance for adefovir for HBV?
LOW to MEDIUM
53
What is the GENETIC BARRIER to resistance for entecavir or tenofovir for HBV?
HIGH
54
What impact does previous exposure to lamivudine have on the utility of ENETECAVIR for HBV?
genetic barrier LOWERED for entecavir
55
What is the most common GENOTYPE of HBV in the UK?
D
56
What is the definition of VIROLOGICAL RESPONSE to antiviral therapy for HEPATITIS B?
UNDETECTABLE HBV DNA at 24 weeks
57
In what THREE situations should HBV be treated in HBV/HIV co-infection?
1) HBV DNA >2000
2) Fibrosis F2 or more
3) CD4 <500 cells
58
Through what mechanism might HIV have a direct effect on fibrogenic process in liver in hepatitis/HIV co-infection?
binding of gp120 to CCR5 on hepatic cells triggers increased COLLAGEN and inflammatory CHEMOKINES
59
What is the 'NORMAL' levels of ALT for women with HBV?
19IU/L
60
What is the 'NORMAL' levels of ALT for men with HBV?
30IU/L
61
Which FOUR drugs used for HBV also have activity against HIV?
lamivudine
emtricitibine
tenofovir
entecavir
62
What consideration may be made when planning HBV treatment if PLW HIV is not on ART?
Use drug with HBV activity but NOT HIV activity
63
What treatment options are available if treating HBV but not HIV?
PEG-IFN
| Adefovir
64
What is the FIRST line treatment for HBV MONOINFECTION?
ENTECAVIR
or
TENOFOVIR
65
What is the criteria for use of PEG-IFN to treat HBV infection?
HbsAg POSITIVE
RAISED ALT
low DNA <2x10to6
minimal fibrosis
66
What complication may occur if PEG-IFN is given to a person with cirrhosis?
DECOMPENSATED liver failure
67
Why can adefovir be used for treatment for HBV despite no ART for HIV?
low dose has no effect on HIV replication therefore does not select out HIV resistance mutations
68
Which is more effective treatment of HBV - adefovir or tenofovir?
TENOFOVIR
69
Which measurement does tenofovir have more of an effect on that adefovir?
HBV DNA (more likely undetectable)
no significant difference on
ALT, seroconversion eAg, sAg loss
70
What is an unsuppressed HBV DNA on adefovir associated with?
higher BASELINE HBV DNA
71
What ART should be used to cover both HBV and HIV?
Tenofovir disoproxil
+/-
lamivudine or emtricitabine
72
Which if preferred additional NRTI for HBV+HIV infection - lamivudine or emtricitabine?
Emtricitabine
(longer half life, more potent, resistance less rapid)
however either 3TC or FTC is sufficient
73
What proportion of people with acute hepatitis B will lose sAg and develop sAb?
60-80%
74
What proportion of people with acute hepatitis B will develop severe or fulminant liver disease?
<0.1%
75
How should severe or fulminant HBV infection be initially managed?
TDF + 3TC or FTC
+/as
ART (if HIV co-infection)
76
How long should treatment for severe or fulminant HBV infection continue?
continue until sAg lost or indefinitely if chronic HBV
| note - old guideline, now if HIV+HBV, continue ART with HBV cover
77
Which hepatitis C genotypes predominate in UK?
ONE (1)
&
THREE (3)
78
What is the prevalence of hepatitis C in the UK?
0.4%
79
In MSM who experience acute hepatitis C infection what is the main mode of transmission?
PerMUCOSAL
| traumatic sex practice + mucosa admin of drugs + concurrent STI
80
What impact does hepatitis C infection have on HIV?
chronic immune ACTIVATION
- immune dysfunction
- cytokine production
- enhanced viral replication
- CD4 apoptosis
81
What is the increased risk of CIRRHOSIS in HCV + HIV co-infection?
TWO-fold higher
82
How does HIV accelerate FIBROSIS in HCV + HIV co-infection?
- HIV virus enters HEPATIC cells
- immune ACTIVATION inducing CYTOKINE release and increase liver INFLAMMATION
- increase TNF induced APOPTOSIS
83
What impact does HCV + HIV co-infection have on the risk of HCC?
INCREASED
younger age
shorter time period
84
What is the investigation of choice for hepatitis C infection?
HCV Ab (if not past infection)
+
HCV PCR
85
Within what time frame is HCV PCR positive after initial infection?
ONE (1) month
86
What proportion of patients with acute hepatitis C infection will have abnormal transaminases?
88% within 3 months
87
What proportion of people with HCV infection will have a negative antibody test still at ONE year after infection?
5%
88
How often should HCV Ab be tested in MSM with high risk of exposure?
3-6 monthly
89
What high risk practices increase risk of exposure to HCV infection in MSM?
UPSI
Recreational drug use
Sharing paraphernalia
90
For whom should ART be started in HCV+HIV co-infection?
ALL (regardless CD4)
91
What is the benefit of starting ART in HCV+HIV co-infection?
improved IMMUNE function
| reduced HIV-immune activation
92
What impact does CD4 cell count have on treatment outcome with PEG-IFN + RBV in HCV+HIV co-infection?
REDUCED treatment SUCCESS
| as CD4 cell count DECLINE
93
Through what mechanism does HIV contribute to the FIBROGENIC process within liver in HCV/HIV co-infection?
DIRECT binding of gp120 to CCR5 receptor on hepatic STELLATE cells
94
If DAA BOCEPREVIR is to be is to be used what is the recommended first line ART?
TDF/FTC + RALTEGRAVIR
95
If DAA TELAPREVIR is to be is to be used what is the recommended first line ART?
TDF/FTC + RALTEGRAVIR
96
What is a suitable alternative ART if DAA TELAPREVIR is to be is to be used?
TDF/FTC
+
boosted ATAZANAVIR
97
Which THREE ART are specifically contraindicated in conjunction with HCV treatment?
Thymidine analogues
- DIDANOSINE
- STAVUDINE
- ZIDOVUDINE
98
For which HCV GENOTYPE are BOCEPREVIR and TELAPREVIR licenced?
ONE (1)
99
What is the definition of sustained virological response (SVR) for HCV treatment?
negative HCV PCR
| 24 weeks after treatment
100
What FOUR factors should be considered prior to HCV treatment?
1) PATIENT
2) VIRAL
3) HEPATIC
4) GENETIC
101
What 'PATIENT' factors should be considered prior to HCV treatment?
```
preference
risk of transmission
risk of re-infection
adherence
age
co-morbidities
DDI
```
102
What 'VIRAL' factors should be considered prior to HCV treatment?
genotype
HCV viral load
IFN responsiveness
103
What 'HEPATIC' factors should be considered prior to HCV treatment?
fibrosis
| risk of decompensation
104
What 'GENETIC' factors should be considered prior to HCV treatment?
IL28B status
105
What is the disadvantage of DAAs BOCEPREVIR and TELAPREVIR?
co-prescription with PEG-IFN & RBV
dosing schedule (TDS)
TOXICITY
DDI
106
What is the TOXICITY profile of BOCEPREVIR?
anaemia
neutropenia
dysgeusia (taste dysfunction)
107
What is the TOXICITY profile of TELAPREVIR?
anaemia
rash
anal discomfort
108
What is the recommended treatment for HCV GENOTYPE 1?
```
PEG-IFN + RIBAVARIN
+
TELAPREVIR
or
BOCEPREVIR
```
109
What is the recommended treatment for HCV GENOTYPE 2 or 3?
PEG-IFN
+
RIBAVARIN
110
How long should PEG-IFN + RBV be give for HCV infection?
48 weeks
111
Which group of patients with HCV infection can have treatment duration reduced to 24 weeks?
NON-CIRRHOTIC
+
rapid response (undetectable at 4 weeks)
112
Which pegylated interferon is more effective in HCV treatment?
pegylated a-interferon 2b
113
Which HCV genotypes respond best to PEG-IFN + RBV?
TWO (2) & THREE (3)
114
How can bone marrow toxicity from IFN or RBV in HCV treatment be managed/supported?
GROWTH factors
- erythropoietin
- granulocyte colony stimulating (GCSF)
115
What is the recommended treatment for HCV GENOTYPE 4?
DEFER until newer treatment
| PEG-IFN + RBV
116
What assessment of virological response should be made if treating HCV GENOTYPE 4?
Check HCV RNA at 12 weeks
| if detectable stop treatment
117
If HCV RNA is DETECTABLE at 12 weeks of treatment for HCV GENOTYPE 4, what should be done?
consider STOP treatment
| low rates of success
118
What is the impact of treatment with PEG-IFN + RBV on HCV genotype 4?
Low response
May need longer >48 weeks if virological response by 12 weeks
Need to stop if no virological response at 12 weeks
119
When should treatment be offered following acute HCV infection?
less than 2 log drop in HCV RNA 4 weeks
or
HCV RNA positive 12 weeks
120
What monitoring should occur if a person has undetectable HCV RNA without treatment?
Test at
4, 12, 24 and 48 weeks
ensure clearance
121
What is the recommended timing of treatment for ACUTE HCV with HIV co-infection?
EARLY treatment
| higher chance of treatment success in acute infection
122
Is the incidence in the UK higher for hepatitis A or E?
E
123
Who is at risk of severe liver disease from hepatitis E?
PREGNANT women
| pre-existing LIVER DISEASE
124
Hepatitis E infection is associated with the consumption of what meat?
wild BOAR
125
What is the limitation of the measurement of HEV antibody in PLW HIV and low CD4 count?
low CD4 count may not develop HEV antibody
126
When is hepatitis E testing recommended for PLW HIV?
elevated transaminases or cirrhosis
+
no other cause found
127
What is the recommended treatment for hepatitis E + HIV co-infection?
optimise ART
128
What is the median survival following first liver decompensation in PLW HIV + HCV vs HCV mono-infection?
13 months
vs
5 years
129
Which hepatitis virus can cause HCC without cirrhosis?
HEPATITIS B (directly carcinogenic)
130
What is the recommended HCC surveillance?
6 monthly liver US and AFP
131
What are potential INDICATIONS for liver TRANSPLANT in PLW HIV?
viral hepatitis CIRRHOSIS +/- HCC
HIV drug induced liver injury
HIV related liver disease (NCPH)
non-HIV liver disease
132
Which group of viral hepatitis has best post-transplant outcomes?
B
