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Spring 2022: Therapeutics IV > Viral Hepatitis > Flashcards

Viral Hepatitis Flashcards

1
Q

HDV requires ______ coinfection for replication and expression.

A

HBV

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2
Q

Which viral hepatitis type occurs primarily in India, Asia, Africa, and Central America?

A

HEV

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3
Q

Hepatitis viruses are all RNA-based, with the exception of which type?

A

HBV (DNA virus)

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4
Q

What symptoms are possible with any type of hepatitis?

A

acute illness with:

  • nausea
  • anorexia
  • fever
  • malaise
  • abdominal pain
  • jaundice
  • elevated transaminases
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5
Q

What is the main mode of transmission for HAV?

A

fecal-oral

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6
Q

What is/are the main mode(s) of transmission for HBV?

A

blood, sexual

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7
Q

What is the main mode of transmission for HBV?

A

blood

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8
Q

Which hepatitis viruses can have perinatal transmission?

A

HBV and HCV

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9
Q

What is the most common risk factor for HAV?

A

direct contact with someone who has HAV

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10
Q

What is the most common risk factor for HBV?

A

being born to an infected mother

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11
Q

What is the most common risk factor for HCV?

A

injection drug use

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12
Q

Which hepatitis viruses can lead to chronic infection?

A

HBV and HCV

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13
Q

What age group is most likely to develop chronic HBV?

A

infants (less of a chance as age increases)

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14
Q

Which type of hepatitis virus has a curative treatment?

A

HCV

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15
Q

Which hepatitis viruses can offer protective immunity?

A

HAV and HBV

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16
Q

For which hepatitis viruses do vaccines exist?

A

HAV and HBV

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17
Q

HAV is classified as what virus type?

A

pirornavirus

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18
Q

HAV is replicated in the _________, excreted in the _________, and shed in the ___________.

A

liver; bile; stool

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19
Q

What is the average incubation period for HAV?

A

28 days

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20
Q

In children <6, is HAV mostly symptomatic or asymptomatic?

A

asymptomatic

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21
Q

In children and older adults is HAV usually symptomatic or asymptomatic?

A

symptomatic (jaundice in > 70%)

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22
Q

HAV onset is ________

A

abrupt

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23
Q

What color stool can occur in HAV?

A

clay-colored

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24
Q

How long do HAV symptoms usually persist?

A

< 2 months (can be prolonged up to 6 months)

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25
Q

True or false: HAV is usually fatal.

A

false

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26
Q

What are the two ways we can diagnose acute HAV?

A
  • IgM anti-HAV in serum (detectable within 5-10 days of symptom onset)
  • HAV RNA in serum or stool
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27
Q

What is the first line treatment for HAV?

A

supportive therapy

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28
Q

What is the minimum age for HAV vaccination?

A

12 months

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29
Q

Are HAV vaccines safe in pregnancy?

A

yes; they are inactivated

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30
Q

Name the 3 HAV vaccines currently available.

A
  • HAVRIX (2 doses)
  • VAQTA (2 doses)
  • TWINRIX (3/4 doses)
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31
Q

Which HAV vaccine also has HBV protection?

A

TWINRIX

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32
Q

Are pre- and post-vaccination serologic tests for HAV generally recommended?

A

no

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33
Q

If exposed to HAV and > 12 months of age, what post-exposure prophylaxis is most appropriate?

A

single-agent vaccine

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34
Q

If exposed to HAV and < 12 months of age, what post-exposure prophylaxis is most appropriate?

A

IM immune globulin (0.1 ml/kg)

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35
Q

If exposed to HAV and > 40 years with increased risk of severe disease, what post-exposure prophylaxis is most appropriate?

A

both the single-agent vaccine and immune globulin

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36
Q

HBV can be classified as a ___________.

A

hepadnavirus

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37
Q

HBV enters though the _________ and replicates in the __________.

A

bloodstream; liver

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38
Q

What is the average incubation period to onset of jaundice for HBV?

A

90 days

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39
Q

What is the average incubation period to onset of abnormal ALT levels for HBV?

A

60 days

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40
Q

What HBV groups will generally present asymptomatically?

A

children < 5 years and newly infected immunosuppressed adults

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41
Q

When present, acute symptoms for HBV are the same as HAV, except for ________________.

A

diarrhea

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42
Q

What does hepatitis B surface antigen (HBsAg) tell us?

A

if the patient is infectious

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43
Q

What does the antibody to hepatitis B surface antigen (Anti-HBs) tell us?

A

if the patient is immune

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44
Q

Which HBV serologic marker does not have a commercially-available assay?

A

hepatitis B core antigen (HBcAg)

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45
Q

What does the IgM class of antibody to hepatitis B core antigen (IgM anti-HBc) tell us?

A

if the patient has been recently exposed to HBV

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46
Q

What does the hepatitis B e antigen (HBeAg) tell us?

A

if the virus is actively replicating

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47
Q

What does the antibody to hepatitis B e antigen (anti-HBe) tell us?

A

if the virus has recently stopped replicating

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48
Q

What treatment is first line for acute HBV infection?

A

no treatment, just supportive care

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49
Q

What are the goals of therapy for chronic HBV management?

A
  • 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)
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50
Q

What initial tests should be run for HBV?

A
  • CBC
  • liver panel
  • INR
  • HBeAg
  • anti-HBe
  • HBV DNA PCR assay
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51
Q

What HBV DNA threshold is associated with increased risk of cirrhosis and HCC, and forms the clinical threshold for most treatment?

A

≥ 2,000 IU/ml (≥10,000 copies/ml)

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52
Q

What is the ALT ULN for males?

A

35 U/L

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53
Q

What is the ALT ULN for females?

A

25 U/L

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54
Q

True or false: treatment can eradicate HBV.

A

false

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55
Q

Describe the ALT, serologic, and HBV DNA makeup of e+ immune-tolerant HBV.

A
  • ALT: normal
  • HBV DNA: HELLA elevated
  • Marker: HBeAg (actively replicating)
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56
Q

Describe the ALT, serologic, and HBV DNA characteristics of e+ immune-active HBV.

A
  • ALT: elevated
  • HBV DNA: elevated
  • Marker: HBeAg (actively replicating)
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57
Q

Describe the ALT, serologic, and HBV DNA characteristics of e- inactive (carrier) HBV.

A
  • ALT: normal
  • HBV DNA: low/undetectable
  • Marker: anti-HBe (recently stopped replicating)
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58
Q

Describe the ALT, serologic, and HBV DNA characteristics of e- immune reactivation HBV.

A
  • ALT: elevated
  • HBV DNA: elevated
  • Marker: anti-HBe (recently stopped replicating)
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59
Q

What phases of HBV should only be monitored?

A
  • e+ immune-tolerant
  • e- inactive (carrier)
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60
Q

When should e+ immune-active phase HBV be treated?

A
  • ALT > 2x ULN
  • HBV DNA > 20,000 IU/ml
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61
Q

When should e- immune reactivation phase HBV be treated?

A
  • ALT > 2x ULN
  • HBV DNA > 2,000 IU/ml
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62
Q

When should e+ cirrhosis phase HBV be treated?

A

HBV DNA > 2,000 IU/ml

63
Q

When should e- cirrhosis phase HBV be treated?

A

HBV DNA > 2,000 IU/ml

64
Q

What is the recommended TDF dose for HBV?

A

300 mg PO QD

65
Q

What is the recommended TAF dose for HBV?

A

25 mg PO QD

66
Q

Why would someone want to prescribe TAF over TDF for HBV?

A

it has less renal impairment and less bone mineral density changes

67
Q

What is the recommended dose of enecavir for HBV in nucleoside-naive patients? For nucleoside-experienced?

A

0.5 mg PO QD for naive

1 mg PO QD for experienced

68
Q

What withdrawal side effect should HBV patients taking a nucleoside analog be aware of?

A

potential ALT flares on withdrawal

69
Q

What are the 1st line nucleoside analogs for HBV?

A
  • tenofovir DF
  • tenofovir AF
  • entecavir
70
Q

What is the only 1st line cytokine for HBV?

A

peginterferon alfa 2a

71
Q

What is the recommended dose of peginterferon alfa 2a for HBV?

A

180 mcg SQ weekly for 48 weeks

72
Q

What is the recommended duration of therapy for nucleoside analogs in HBV?

A

for most, indefinite

73
Q

In what groups is peginterferon alfa 2a contraindicated for HBV?

A
  • 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
Q

Why are lamivudine, adefovir, and telbivudine not 1st line for HBV?

A

high resistance rates

75
Q

Why is interferon alfa 2b not 1st line for HBV?

A

more frequent dosing (either daily or thrice weekly)

76
Q

What side effects are associated with peginterferon alfa 2a?

A
  • flu-like symptoms
  • fatigue
  • mood disturbances
  • cytopenia
  • autoimmune disorders
  • anorexia
77
Q

What is the pregnancy category for peginterferon alfa 2a?

A

C

78
Q

What on-treatment monitoring is required for peginterferon alfa 2a?

A
  • CBC (monthly-every 3 months)
  • TSH (every 3 months)
  • clinical monitoring for autoimmune, ischemic, neuropsychiatric, and infectious complications
79
Q

What side effects are associated with entecavir?

A

lactic acidosis (decompensated cirrhosis only)

80
Q

What is the pregnancy category for entecavir?

A

C

81
Q

What on-treatment monitoring is required for entecavir?

A
  • lactic acid (if clinical concern)
  • test for HIV before starting
82
Q

What side effects are associated with tenofovir DF?

A
  • nephropathy
  • Fanconi syndrome
  • osteomalacia
  • lactic acidosis
83
Q

What pregnancy category is tenofovir DF?

A

B

84
Q

What on-treatment monitoring is required for tenofovir DF?

A
  • 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
Q

What side effect is associated with tenofovir AF?

A

lactic acidosis

86
Q

What pregnancy category is tenofovir AF?

A

unknown

87
Q

What on-treatment monitoring is recommended for tenofovir AF?

A
  • 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
Q

True or false: all HBV medications should be renally dose-adjusted in patients with dysfunction.

A

true

89
Q

Which HBV medication can cause pancreatitis?

A

lamivudine

90
Q

How often should ALT be monitored in immune tolerant HBV patients?

A

every 3-6 months

91
Q

How often should eAg be monitored in immune tolerant HBV patients?

A

every 6-12 months

92
Q

How often should ALT be monitored in e- inactive HBV patients?

A

every 6-12 months

93
Q

For patients on therapy, HBV DNA levels should be monitored every ___ months on NA therapy until undetectable, then every _______ months thereafter.

A

3; 3-6

94
Q

How often should you monitor patients for recurrent viremia, ALT flares, seroreversion, and decompensation after stopping HBV therapy?

A

every 3 months for at least 1 year

95
Q

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.

A

6

96
Q

What anti-HBV drug is recommended for pregnant women in order to minimize perinatal transmission?

A

tenofovir DF beginning at week 28-32 of gestation (if HBV DNA > 200,000)

97
Q

True or false: infants born to mothers on chronic HBV therapy do not need to receive vaccination or post-exposure prophylaxis.

A

false; should receive HBV vaccination +/- immunoglobulin

98
Q

What drug combination is frequently used when someone has HBV and HIV coinfection?

A

emtricitabine/tenofovir (Truvada, Descovy)

99
Q

All infants should be vaccinated against HBV, beginning at _______.

A

birth

100
Q

Are HBV vaccines safe in pregnancy?

A

yes; all available ones are inactivated

101
Q

What single agent HBV vaccines are available?

A
  • ENGERIX-B
  • RECOMBIVAX HB
  • HEPLISAV-B
102
Q

What combination vaccines are available for HBV?

A
  • PEDIARIX (combined with diphtheria, tetanus, acellular pertussis, polio)
  • TWINRIX (combined with hepatitis A)
103
Q

When is HBV post-vaccination testing for immunity recommended?

A
  • 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
Q

HCV is classified as a __________.

A

flavivirus

105
Q

HCV is differentiated into how many different genotypes?

A

7

106
Q

What are the most common genotypes in the US?

A

1a and 1b, followed by 2 and 3

107
Q

What is the average time from exposure to symptom onset for HCV?

A

4-12 weeks

108
Q

Chronic HCV infection is defined how?

A

persistently detectable HCV for 6+ months

109
Q

Although chronic HCV patients have few, if any, symptoms, what are the two most common?

A

chronic fatigue and depression

110
Q

Locate the hepatitis C guidelines published by the American Association for the Study of Liver Diseases & the Infectious Diseases Society of America.

A

www.hcvguidelines.org

111
Q

What are the goals of therapy for HCV management?

A
  • 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
Q

What is the only circumstance in which you would not recommend chronic HCV treatment?

A

those with short (< 12 months) life expectancy unrelated to liver disease

113
Q

All DAAs carry a warning of risk of _____________.

A

HBV reactivation (check HBV serologies prior to DAA initiation)

114
Q

All NS3/4A protease inhibitors are potent CYP3A4 ____________.

A

inhibitors

115
Q

Which NS3/4A protease inhibitors are currently on the market for HCV treatment?

A
  • grazoprevir
  • glecaprevir
  • voxilaprevir
116
Q

What is the recommended dose of grazoprevir for HCV?

A

100 mg PO QD with or without food

117
Q

What is the recommended dose of glecaprevir for HCV?

A

300 mg PO QD with food

118
Q

What is the recommended dose of voxilaprevir for HCV?

A

100 mg PO QD with food

119
Q

What adverse effects are associated with grazoprevir?

A
  • fatigue
  • headache
  • nausea
  • anemia
  • ALT elevations
120
Q

When should patients in grazoprevir for HCV have their ALT checked?

A

8 weeks (discontinue if > 5x ULN)

121
Q

When is grazoprevir for HCV contraindicated?

A

Child-Pugh B or C

122
Q

What side effects are associated with glecaprevir?

A
  • headache
  • fatigue
123
Q

Which HCV genotypes is glecaprevir approved for?

A

all genotypes

124
Q

When is glecaprevir use for HCV contraindicated?

A

Child-Pugh C

125
Q

What adverse effects are associated with voxilaprevir for HCV?

A
  • headache
  • fatigue
  • diarrhea
  • nausea
126
Q

What is the primary scenario in which voxilaprevir would be the nucleoside analog of choice for HCV?

A

patients who have been previously treated with an NS5A replication complex inhibitor

127
Q

What is the only currently available NS5B inhibitor for HCV management?

A

sofosbuvir

128
Q

What is the recommended sofosbuvir dose for HCV?

A

400 mg PO QD with or without food

129
Q

What adverse effects are associated with sofosbuvir?

A
  • fatigue
  • headache
130
Q

What drug should not be administered with sofosbuvir?

A

amiodarone (symptomatic bradycadia)

131
Q

Does sofosbuvir need to be hepatically dose adjusted?

A

no

132
Q

What NS5A replication complex inhibitors are currently on the market for HCV treatment?

A
  • ledipasvir
  • elbasvir
  • velpatasvir
  • pibrentasvir
133
Q

NS5A replication complex inhibitors have a _______ barrier to resistance.

A

low

134
Q

What is the recommended dose of ledipasvir for HCV?

A

90 mg PO QD with or without food

135
Q

What adverse effects are associated with ledipasvir?

A
  • fatigue
  • headache
136
Q

Does ledipasvir need to be hepatically dose adjusted?

A

no

137
Q

What is the recommended HCV dose for elbasvir?

A

100 mg PO QD with or without food

138
Q

What test must be done before initiating elbasvir in patients with genotype 1a?

A

an NS5A genotype must be performed to screen for presence of resistance-associated substitutions (RASs) at baseline

139
Q

How is elbasvir dosing affected by mutations at codons 28, 30, 31, or 93?

A

extended 16-week course + ribavirin

140
Q

What is the recommended velpatasvir dose for HCV?

A

100 mg PO QD with or without food

141
Q

What adverse effects are associated with velpatasvir?

A
  • fatigue
  • headache
142
Q

What test must be performed prior to using velpatasvir in compensated cirrhotic patients with genotype 3?

A

NS5A genotype must be performed to screen for presence of the Y93H substitution

143
Q

How does Y93H substitution effect velpatasvir dosing?

A

must add ribavirin or voxilaprevir

144
Q

Does velpatasvir need to be hepatically dose adjusted?

A

no

145
Q

What is the recommended dose of pibrentasvir for HCV?

A

120 mg PO QD with food

146
Q

List the FDA-approved DAAs for HCV.

A
  • ELB/GRZ
  • PIB/GLE
  • VEL/SOF/VOX
  • SOF
  • LVD/SOF
  • VEL/SOF
147
Q

What is the only DAA that requires 3 tablets daily?

A

pibrentasvir/glecaprevir (Mavyret)

148
Q

What are the recommended doses for ribavirin?

A
  • < 75 kg = 1000 mg in 2 divided doses with food
  • 75 kg+ = 1200 mg in 2 divided doses with food
149
Q

Ribavirin is a _______ analog.

A

guanosine

150
Q

What is the most prominent adverse effect of ribavirin?

A

hemolytic anemia

151
Q

True or false: ribavirin is safe in pregnancy.

A

false; it is a teratogen (category X)

152
Q

In what groups is ribavirin contraindicated?

A

CrCl < 50 ml/min

153
Q

At what Hgb level should the ribavirin dose be decreased?

A

< 10 g/dl

154
Q

At what Hgb level should ribavirin be discontinued?

A

< 8.5 g/dl

Spring 2022: Therapeutics IV (12 decks)

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