Viral Hepatitis Flashcards
1
Q
HDV requires ______ coinfection for replication and expression.
A
HBV
2
Q
Which viral hepatitis type occurs primarily in India, Asia, Africa, and Central America?
A
HEV
3
Q
Hepatitis viruses are all RNA-based, with the exception of which type?
A
HBV (DNA virus)
4
Q
What symptoms are possible with any type of hepatitis?
A
acute illness with:
- nausea
- anorexia
- fever
- malaise
- abdominal pain
- jaundice
- elevated transaminases
5
Q
What is the main mode of transmission for HAV?
A
fecal-oral
6
Q
What is/are the main mode(s) of transmission for HBV?
A
blood, sexual
7
Q
What is the main mode of transmission for HBV?
A
blood
8
Q
Which hepatitis viruses can have perinatal transmission?
A
HBV and HCV
9
Q
What is the most common risk factor for HAV?
A
direct contact with someone who has HAV
10
Q
What is the most common risk factor for HBV?
A
being born to an infected mother
11
Q
What is the most common risk factor for HCV?
A
injection drug use
12
Q
Which hepatitis viruses can lead to chronic infection?
A
HBV and HCV
13
Q
What age group is most likely to develop chronic HBV?
A
infants (less of a chance as age increases)
14
Q
Which type of hepatitis virus has a curative treatment?
A
HCV
15
Q
Which hepatitis viruses can offer protective immunity?
A
HAV and HBV
16
Q
For which hepatitis viruses do vaccines exist?
A
HAV and HBV
17
Q
HAV is classified as what virus type?
A
pirornavirus
18
Q
HAV is replicated in the _________, excreted in the _________, and shed in the ___________.
A
liver; bile; stool
19
Q
What is the average incubation period for HAV?
A
28 days
20
Q
In children <6, is HAV mostly symptomatic or asymptomatic?
A
asymptomatic
21
Q
In children and older adults is HAV usually symptomatic or asymptomatic?
A
symptomatic (jaundice in > 70%)
22
Q
HAV onset is ________
A
abrupt
23
Q
What color stool can occur in HAV?
A
clay-colored
24
Q
How long do HAV symptoms usually persist?
A
< 2 months (can be prolonged up to 6 months)
25
True or false: HAV is usually fatal.
false
26
What are the two ways we can diagnose acute HAV?
* **IgM anti-HAV in serum** (detectable within 5-10 days of symptom onset)
* **HAV RNA in serum or stool**
27
What is the first line treatment for HAV?
supportive therapy
28
What is the minimum age for HAV vaccination?
12 months
29
Are HAV vaccines safe in pregnancy?
yes; they are inactivated
30
Name the 3 HAV vaccines currently available.
* HAVRIX (2 doses)
* VAQTA (2 doses)
* TWINRIX (3/4 doses)
31
Which HAV vaccine also has HBV protection?
TWINRIX
32
Are pre- and post-vaccination serologic tests for HAV generally recommended?
no
33
If exposed to HAV and \> 12 months of age, what post-exposure prophylaxis is most appropriate?
single-agent vaccine
34
If exposed to HAV and \< 12 months of age, what post-exposure prophylaxis is most appropriate?
IM immune globulin (0.1 ml/kg)
35
If exposed to HAV and \> 40 years with increased risk of severe disease, what post-exposure prophylaxis is most appropriate?
both the single-agent vaccine and immune globulin
36
HBV can be classified as a \_\_\_\_\_\_\_\_\_\_\_.
hepadnavirus
37
HBV enters though the _________ and replicates in the \_\_\_\_\_\_\_\_\_\_.
bloodstream; liver
38
What is the average incubation period to onset of jaundice for HBV?
90 days
39
What is the average incubation period to onset of abnormal ALT levels for HBV?
60 days
40
What HBV groups will generally present asymptomatically?
children \< 5 years and newly infected immunosuppressed adults
41
When present, acute symptoms for HBV are the same as HAV, except for \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.
diarrhea
42
What does hepatitis B surface antigen (HBsAg) tell us?
if the patient is infectious
43
What does the antibody to hepatitis B surface antigen (Anti-HBs) tell us?
if the patient is immune
44
Which HBV serologic marker does not have a commercially-available assay?
hepatitis B core antigen (HBcAg)
45
What does the IgM class of antibody to hepatitis B core antigen (IgM anti-HBc) tell us?
if the patient has been recently exposed to HBV
46
What does the hepatitis B e antigen (HBeAg) tell us?
if the virus is actively replicating
47
What does the antibody to hepatitis B e antigen (anti-HBe) tell us?
if the virus has recently stopped replicating
48
What treatment is first line for acute HBV infection?
no treatment, just supportive care
49
What are the goals of therapy for chronic HBV management?
* achieve sustained suppression of HBV replication
* remission of liver disease
* prevent cirrhosis, hepatic failure, and HCC
* attain a functional cure (HBsAg loss +/- anti-HBe gain)
50
What initial tests should be run for HBV?
* CBC
* **liver panel**
* INR
* **HBeAg**
* anti-HBe
* **HBV DNA PCR assay**
51
What HBV DNA threshold is associated with increased risk of cirrhosis and HCC, and forms the clinical threshold for most treatment?
**≥ 2,000 IU/ml** (≥10,000 copies/ml)
52
What is the ALT ULN for males?
35 U/L
53
What is the ALT ULN for females?
25 U/L
54
True or false: treatment can eradicate HBV.
false
55
Describe the ALT, serologic, and HBV DNA makeup of **e+ immune-tolerant** HBV.
* ALT: normal
* HBV DNA: HELLA elevated
* Marker: HBeAg (actively replicating)
56
Describe the ALT, serologic, and HBV DNA characteristics of **e+ immune-active** HBV.
* ALT: elevated
* HBV DNA: elevated
* Marker: HBeAg (actively replicating)
57
Describe the ALT, serologic, and HBV DNA characteristics of **e- inactive (carrier)** HBV.
* ALT: normal
* HBV DNA: low/undetectable
* Marker: anti-HBe (recently stopped replicating)
58
Describe the ALT, serologic, and HBV DNA characteristics of **e- immune reactivation** HBV.
* ALT: elevated
* HBV DNA: elevated
* Marker: anti-HBe (recently stopped replicating)
59
What phases of HBV should only be monitored?
* e+ immune-tolerant
* e- inactive (carrier)
60
When should e+ immune-active phase HBV be treated?
* ALT \> 2x ULN
* HBV DNA \> 20,000 IU/ml
61
When should e- immune reactivation phase HBV be treated?
* ALT \> 2x ULN
* HBV DNA \> 2,000 IU/ml
62
When should e+ cirrhosis phase HBV be treated?
HBV DNA \> 2,000 IU/ml
63
When should e- cirrhosis phase HBV be treated?
HBV DNA \> 2,000 IU/ml
64
What is the recommended TDF dose for HBV?
300 mg PO QD
65
What is the recommended TAF dose for HBV?
25 mg PO QD
66
Why would someone want to prescribe TAF over TDF for HBV?
it has less renal impairment and less bone mineral density changes
67
What is the recommended dose of enecavir for HBV in nucleoside-naive patients? For nucleoside-experienced?
0.5 mg PO QD for naive
1 mg PO QD for experienced
68
What withdrawal side effect should HBV patients taking a nucleoside analog be aware of?
potential ALT flares on withdrawal
69
What are the 1st line nucleoside analogs for HBV?
* tenofovir DF
* tenofovir AF
* entecavir
70
What is the only 1st line cytokine for HBV?
peginterferon alfa 2a
71
What is the recommended dose of peginterferon alfa 2a for HBV?
180 mcg **SQ** weekly for 48 weeks
72
What is the recommended duration of therapy for nucleoside analogs in HBV?
for most, indefinite
73
In what groups is peginterferon alfa 2a contraindicated for HBV?
* **decompensated liver disease**
* history of/current psychosis
* severe depression
* neutropenia
* thrombocytopenia
* symptomatic heart disease
* uncontrolled seizures
* *also use caution in patients with autoimmune disorders*
74
Why are lamivudine, adefovir, and telbivudine not 1st line for HBV?
high resistance rates
75
Why is interferon alfa 2b not 1st line for HBV?
more frequent dosing (either daily or thrice weekly)
76
What side effects are associated with peginterferon alfa 2a?
* flu-like symptoms
* fatigue
* mood disturbances
* cytopenia
* autoimmune disorders
* anorexia
77
What is the pregnancy category for peginterferon alfa 2a?
C
78
What on-treatment monitoring is required for peginterferon alfa 2a?
* CBC (monthly-every 3 months)
* TSH (every 3 months)
* clinical monitoring for autoimmune, ischemic, neuropsychiatric, and infectious complications
79
What side effects are associated with entecavir?
lactic acidosis (decompensated cirrhosis only)
80
What is the pregnancy category for entecavir?
C
81
What on-treatment monitoring is required for entecavir?
* lactic acid (if clinical concern)
* test for HIV before starting
82
What side effects are associated with tenofovir DF?
* nephropathy
* Fanconi syndrome
* osteomalacia
* lactic acidosis
83
What pregnancy category is tenofovir DF?
B
84
What on-treatment monitoring is required for tenofovir DF?
* CrCl at baseline
* CrCl, serum phosphate, urine glucose, urine protein at least annually (if risk for renal impairment)
* bone density at baseline (if risk for osteopenia or history of fracture)
* lactic acid (if clinical concern)
* test for HIV before starting
85
What side effect is associated with tenofovir AF?
lactic acidosis
86
What pregnancy category is tenofovir AF?
unknown
87
What on-treatment monitoring is recommended for tenofovir AF?
* CrCl, serum creatinine, serum phosphate, urine glucose, urine protein at least annually (if risk for renal impairment)
* lactic acid (if clinical concern)
* test for HIV before starting
88
True or false: all HBV medications should be renally dose-adjusted in patients with dysfunction.
true
89
Which HBV medication can cause pancreatitis?
lamivudine
90
How often should ALT be monitored in immune tolerant HBV patients?
every 3-6 months
91
How often should eAg be monitored in immune tolerant HBV patients?
every 6-12 months
92
How often should ALT be monitored in e- inactive HBV patients?
every 6-12 months
93
For patients on therapy, HBV DNA levels should be monitored every ___ months on NA therapy until undetectable, then every _______ months thereafter.
3; 3-6
94
How often should you monitor patients for recurrent viremia, ALT flares, seroreversion, and decompensation after stopping HBV therapy?
every 3 months for at least 1 year
95
All HBsAg+ patients with cirrhosis and high risk non-cirrhotics (Asian or black men over 40, Asian women over 50, and those with first degree relatives with HCC) should receive HCC surveillance every ___ months (abdominal ultrasound + AFP), even if on treatment.
6
96
What anti-HBV drug is recommended for pregnant women in order to minimize perinatal transmission?
tenofovir DF beginning at week 28-32 of gestation (if HBV DNA \> 200,000)
97
True or false: infants born to mothers on chronic HBV therapy do not need to receive vaccination or post-exposure prophylaxis.
false; should receive HBV vaccination +/- immunoglobulin
98
What drug combination is frequently used when someone has HBV and HIV coinfection?
**emtricitabine/tenofovir** (*Truvada, Descovy*)
99
All infants should be vaccinated against HBV, beginning at \_\_\_\_\_\_\_.
birth
100
Are HBV vaccines safe in pregnancy?
yes; all available ones are inactivated
101
What single agent HBV vaccines are available?
* ENGERIX-B
* RECOMBIVAX HB
* HEPLISAV-B
102
What combination vaccines are available for HBV?
* PEDIARIX (combined with diphtheria, tetanus, acellular pertussis, polio)
* TWINRIX (combined with hepatitis A)
103
When is HBV post-vaccination testing for immunity recommended?
* infants born to HBsAg-positive mothers
* healthcare and public safety workers with high exposure risk
* immunocompromised patients (plus those on hemodialysis)
* sex partners of chronic HBV patients
104
HCV is classified as a \_\_\_\_\_\_\_\_\_\_.
flavivirus
105
HCV is differentiated into how many different genotypes?
7
106
What are the most common genotypes in the US?
1a and 1b, followed by 2 and 3
107
What is the average time from exposure to symptom onset for HCV?
4-12 weeks
108
Chronic HCV infection is defined how?
persistently detectable HCV for 6+ months
109
Although chronic HCV patients have few, if any, symptoms, what are the two most common?
chronic fatigue and depression
110
Locate the hepatitis C guidelines published by the American Association for the Study of Liver Diseases & the Infectious Diseases Society of America.
www.hcvguidelines.org
111
What are the goals of therapy for HCV management?
* Obtain virological cure by achieving a sustained virological response (SVR) – HCV RNA undetectable 12 weeks after cessation of treatment
* Prevent complications (cirrhosis, HCC) and death
112
What is the only circumstance in which you would not recommend chronic HCV treatment?
those with short (\< 12 months) life expectancy unrelated to liver disease
113
All DAAs carry a warning of risk of \_\_\_\_\_\_\_\_\_\_\_\_\_.
HBV reactivation (check HBV serologies prior to DAA initiation)
114
All NS3/4A protease inhibitors are potent CYP3A4 \_\_\_\_\_\_\_\_\_\_\_\_.
inhibitors
115
Which NS3/4A protease inhibitors are currently on the market for HCV treatment?
* grazoprevir
* glecaprevir
* voxilaprevir
116
What is the recommended dose of grazoprevir for HCV?
100 mg PO QD **with or without food**
117
What is the recommended dose of glecaprevir for HCV?
300 mg PO QD **with food**
118
What is the recommended dose of voxilaprevir for HCV?
100 mg PO QD **with food**
119
What adverse effects are associated with grazoprevir?
* fatigue
* headache
* nausea
* anemia
* ALT elevations
120
When should patients in grazoprevir for HCV have their ALT checked?
8 weeks (discontinue if \> 5x ULN)
121
When is grazoprevir for HCV contraindicated?
Child-Pugh B or C
122
What side effects are associated with glecaprevir?
* headache
* fatigue
123
Which HCV genotypes is glecaprevir approved for?
all genotypes
124
When is glecaprevir use for HCV contraindicated?
Child-Pugh C
125
What adverse effects are associated with voxilaprevir for HCV?
* headache
* fatigue
* diarrhea
* nausea
126
What is the primary scenario in which voxilaprevir would be the nucleoside analog of choice for HCV?
patients who have been previously treated with an NS5A replication complex inhibitor
127
What is the only currently available NS5B inhibitor for HCV management?
sofosbuvir
128
What is the recommended sofosbuvir dose for HCV?
400 mg PO QD **with or without food**
129
What adverse effects are associated with sofosbuvir?
* fatigue
* headache
130
What drug should not be administered with sofosbuvir?
amiodarone (symptomatic bradycadia)
131
Does sofosbuvir need to be hepatically dose adjusted?
no
132
What NS5A replication complex inhibitors are currently on the market for HCV treatment?
* ledipasvir
* elbasvir
* velpatasvir
* pibrentasvir
133
NS5A replication complex inhibitors have a _______ barrier to resistance.
low
134
What is the recommended dose of ledipasvir for HCV?
90 mg PO QD **with or without food**
135
What adverse effects are associated with ledipasvir?
* fatigue
* headache
136
Does ledipasvir need to be hepatically dose adjusted?
no
137
What is the recommended HCV dose for elbasvir?
100 mg PO QD **with or without food**
138
What test must be done before initiating elbasvir in patients with genotype 1a?
an NS5A genotype must be performed to screen for presence of resistance-associated substitutions (RASs) at baseline
139
How is elbasvir dosing affected by mutations at codons 28, 30, 31, or 93?
extended 16-week course + ribavirin
140
What is the recommended velpatasvir dose for HCV?
100 mg PO QD **with or without food**
141
What adverse effects are associated with velpatasvir?
* fatigue
* headache
142
What test must be performed prior to using velpatasvir in compensated cirrhotic patients with genotype 3?
NS5A genotype must be performed to screen for presence of the Y93H substitution
143
How does Y93H substitution effect velpatasvir dosing?
must add ribavirin or voxilaprevir
144
Does velpatasvir need to be hepatically dose adjusted?
no
145
What is the recommended dose of pibrentasvir for HCV?
120 mg PO QD **with food**
146
List the FDA-approved DAAs for HCV.
* ELB/GRZ
* PIB/GLE
* VEL/SOF/VOX
* SOF
* LVD/SOF
* VEL/SOF
147
What is the only DAA that requires 3 tablets daily?
pibrentasvir/glecaprevir (*Mavyret*)
148
What are the recommended doses for ribavirin?
* \< 75 kg = 1000 mg in 2 divided doses **with food**
* 75 kg+ = 1200 mg in 2 divided doses **with food**
149
Ribavirin is a _______ analog.
guanosine
150
What is the most prominent adverse effect of ribavirin?
hemolytic anemia
151
True or false: ribavirin is safe in pregnancy.
false; it is a teratogen (category X)
152
In what groups is ribavirin contraindicated?
CrCl \< 50 ml/min
153
At what Hgb level should the ribavirin dose be decreased?
\< 10 g/dl
154
At what Hgb level should ribavirin be discontinued?
\< 8.5 g/dl
