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PHAR255 > Liver 2 > Flashcards

Liver 2 Flashcards

Hepatitis

1
Q

What are the various presentations of hepatitis?

A

asymptomatic
-AST & ALT
acute hepatitis
-flu-like, abdominal pain, jaundice, scleral icterus, pale stools, dark urine
acute fulminant hepatitis
-rare, but may be fatal
chronic persistent hepatitis
-delayed recovery with minimal liver damage but failure to develop antibody (carrier state)
chronic active hepatitis
-progressive liver damage, failure to develop antibody, may be asymptomatic

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2
Q

What kind of virus is hepatitis A?

A

RNA virus

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3
Q

How is hepatitis A transmitted?

A

fecal-oral route
-more likely in travel to countries with high rates, poor conditions & hygiene, overcrowding; contaminated food or water

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4
Q

What are the symptoms of hepatitis A?

A

> 70% of pts symptomatic with fever, jaundice, and scleral icterus, hepatomegaly on physical exam
less common: splenomegaly, skin rash, arthralgia

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5
Q

How long does it take for clinical manifestations of hepatitis A to appear? How long do the symptoms last?

A

time from exposure to clinical manifestations is ~30 days
symptoms usually last ~ 3 months

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6
Q

What is the sequelae of hepatitis A?

A

fulminant hepatitis
-very rare
mortality rate is < 0.1% due to hep A

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7
Q

True or false: hepatitis A is a chronic infection

A

false

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8
Q

What is the treatment for hepatitis A?

A

supportive
-healthy diet, maintaining fluids, avoiding hepatotoxic drugs and EtOH
-no clear role for pharmacologic therapy

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9
Q

How can hepatitis A be prevented?

A

vaccine for high-risk individuals (2 doses, 6 months apart)

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10
Q

What is post-exposure prophylaxis for hepatitis A?

A

vaccine given within 14 days of exposure
Ig given ASAP if vaccine unavailable, contraindicated or patient < 1

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11
Q

What are the serologic markers of hepatitis A?

A

total anti-HAV
-represents total IgG and IgM antibodies to HAV
+ anti-HAV IgG represents immunity from vaccination or previous exposure
+ anti-HAV IgM indicates acute HAV infection

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12
Q

What kind of virus is hepatitis B?

A

DNA virus

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13
Q

How is hepatitis B transmitted?

A

perinatal
sexual
blood

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14
Q

True or false: hepatitis B is preventable through vaccine

A

true

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15
Q

What are the symptoms of hepatitis B?

A

70% of patients are anicteric or subclinical
younger pts more likely to be asymptomatic
sx: jaundice, dark urine, white stool, abdominal pain, fatigue, fever, chills, loss of appetite, pruritus

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16
Q

Is hepatitis B chronic?

A

depends
-varies with age

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17
Q

What is the sequelae of hepatitis B?

A

fulminant hepatitis
cirrhosis
hepatic carcinoma

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18
Q

What are the serological markers of hepatitis B?

A

HBsAg (HBV surface antigen)
-+ indicates HBV infection, acute or chronic
anti-HBs (antibody to HBV surface antigen)
-marker of HBV immunity
-HBsAg and anti-HBs are present, HBV infection persists
HBV-DNA
-marker of viral replication/infectivity
-monitoring treatment of chronic HBV

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19
Q

Describe screening for hepatitis B.

A

universal screening at least once for > 18
high risk groups

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20
Q

When is treatment for hepatitis B recommended?

A

treat during immune active HBV (increased HBV-DNA & ALT; liver inflammation)

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21
Q

What are the two classes of drugs used to treat hepatitis B?

A

interferon
-PEG interferon alfa-2
nucleoside analogues
-lamivudine
-tenofovir, entecavir
-adefovir

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22
Q

What are the treatment goals of hepatitis B?

A

permanent suppression/elimination of virus
-permanent suppression because elimination is not always possible (undetectable HBV DNA level and normalization of liver enzymes)
-functional cure is the goal but is rare
prevent cirrhosis, liver failure and hepatocellular carcinoma

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23
Q

What is the definition of ‘functional cure of hepatitis B’?

A

HBsAg loss with or without appearance of antibodies to HBsAg

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24
Q

What are interferons?

A

cytokines with direct antiviral and immunomodulatory properties

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25
Q

How long is hepatitis B therapy with interferons?

A

16-48 week course
-30% successful in developing immunity

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26
Q

What are the advantages of interferons?

A

shorter course of therapy
absence of resistance
a chance at full seroconversion

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27
Q

In which patients are interferons used?

A

patients with lower HBV DNA levels and elevated aminotransferase values

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28
Q

What are the disadvantages of interferons?

A

CI in decompensated cirrhosis
-increased risk of life-threatening infections and worsening hepatic dysfunction
SC injection
many side effects

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29
Q

What is the response rate with nucleoside analogues?

A

> 90% response
-10-15% success in developing immunity

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30
Q

What are the advantages of nucleoside analogues?

A

safer
fewer side effects
oral

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31
Q

What are the disadvantages of nucleoside analogues?

A

chronic therapy
-endpoint: seroconversion in 12 months
-can take years, indefinite therapy in some
drug resistance
adjust in renal dysfunction

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32
Q

What is the MOA of lamivudine?

A

pyrimidine nucleoside analogue inhibitor of HBV

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33
Q

What was the first oral agent approved for hepatitis B?

A

lamivudine

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34
Q

What is the safety and efficacy of lamivudine?

A

well tolerated and effective but resistance rates approaching 70% at 4 years
-no longer DOC for hep B

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35
Q

What is the main use of lamivudine?

A

prophylaxis (hep B) for those on immunosuppression
pregnant women

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36
Q

What is the MOA of adefovir?

A

nucleotide analogue

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37
Q

What is the efficacy of adefovir?

A

less potent & does not achieve viral suppression in most in the first year
-not the DOC for hep B

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38
Q

What is the use of adefovir?

A

add on in lamivudine resistance

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39
Q

What are the side effects of adefovir?

A

nephrotoxicity
hypophosphatemia

40
Q

What is the DOC for hepatitis B?

A

tenofovir
-licensed for HIV and potent HBV
-DOC in lamivudine resistant and HIV/HBV coinfection
entecavir
-more effective than lamivudine but dont use in lamivudine resistance

41
Q

How many salts are there for tenofovir?

A

two
-tenofovir disoproxil fumarate (TDF)
-tenofovir alafenamide (TAF)
both are prodrugs of tenofovir disphosphate
TAF produces higher levels of tenofovir disphosphate in cells than TDF and can be administered in lower doses

42
Q

What is the MOA of tenofovir?

A

purine nucleotide reverse transcriptase inhibitor

43
Q

Which hepatitis B drug is the most potent and has the lowest chance of resistance?

A

tenofovir

44
Q

What is the MOA of entecavir?

A

selective guanisine analogue and potent inhibitor of HBV DNA replication

45
Q

When is combo therapy used for hepatitis B?

A

people with cirrhosis who have resistance
-may have a fatal flare
add on approach

46
Q

What kind of virus is hepatitis C?

A

single-stranded RNA virus

47
Q

How is hepatitis C transmitted?

A

perinatal, sexual, blood
-parenteral most effective
-sexual transmission very low

48
Q

True or false: there is a vaccine available for hepatitis C

A

false

49
Q

What are the symptoms of hepatitis C?

A

70% of patients are asymptomatic
if symptoms occur:
-jaundice
-dark urine
-white stool
-abdominal pain
-fatigue
-fever
-loss of appetite
-pruritis

50
Q

What is the sequelae of hepatitis C?

A

chronic disease (75%; 25% spontaneously resolve)
cirrhosis
hepatocellular carcinoma

51
Q

How long could it take for the first clinical presentation of hepatitis C?

A

20-30y post exposure

52
Q

Which hepatitis C genotypes are most common in Canada?

A

1a, 1b, 2, 3
there are many different genotypes of hepatitis C

53
Q

What are the serological marker for hepatitis C?

A

anti-HCV (antibody to HCV)
-indicates infection, either acute or chronic
-remains positive for life despite clearance of infection
-need HCVRNA to confirm acute infection
HCV RNA PCR indicates virus replication activity (appears at start of infection and level may fluctuate)
screen high risk individuals annually with an anti-HCV

54
Q

What was the traditional primary objective for hepatitis C treatment? What is the objective today?

A

traditionally:
-complete elimination of virus as undetectable HCV RNA at least 24-48wks post-treatment
today:
-8 to 12 weeks

55
Q

What was the traditional treatment of hepatitis C?

A

interferon and ribavirin combo
-treatment has since evolved

56
Q

What is the MOA of ribavirin?

A

nucleoside analogue

57
Q

What is the dosing frequency of ribavirin?

A

po BID

58
Q

What is the antiviral spectrum of ribavirin?

A

very broad spectrum
-DNA, RNA, influenza, flavaviruses, viral hemorrhagic fevers

59
Q

What are the side effects of ribavirin?

A

hemolytic anemia, rash, depression, fatigue, insomnia
*teratogen: male & female (contraception x 6mo post-tx)

60
Q

What is the tolerability of ribavirin + IFN?

A

nasty side effects

61
Q

Which genotype of hepatitis C does simeprevir target?

A

genotype 1

62
Q

What is the dosing and side effects of simeprevir?

A

OD dosing with food
AE: rash, pruritis, nausea, photosensitivity

63
Q

What is the problem with simeprevir?

A

resistance

64
Q

What is the efficacy of sofosbuvir?

A

raises average cure rate of chronic HCV type 1 to > 90% (except g3)
must be used with either:
-PEG IFN & RBV in genotype 1 or 4
-RBV alone for genotype 2 & 3
-ledispavir in genotype 1

65
Q

What is the treatment duration with sofosbuvir?

A

12-24 wks (depending on strain)

66
Q

What are the drug interactions of sofosbuvir?

A

substrate of P-gp
-induces may decrease levels
bradycardia when given with amiodarone

67
Q

What are the benefits of sofosbuvir?

A

first po antiviral to be used without IFN
OD dosing, no meal restrictions
few specific AE
less DI, resistance
not CI in advanced liver disease

68
Q

What are the cons of sofosbuvir?

A

accumulates in renal disease
not great results in g3

69
Q

Which drugs are in Harvoni?

A

ledipasvir & sofosbuvir

70
Q

What is an important drug interaction of Harvoni?

A

co-administration with PPIs
-decreased absorption

71
Q

What are the side effects of Harvoni?

A

mild to moderate in severity
fatigue
headache
insomnia
nausea

72
Q

What are the drugs in Zepatier?

A

grazoprevir & elbasavir

73
Q

Which patient population has Zepatier been studied in?

A

difficult to treat or lack of data in literature (PWID, renal)

74
Q

What are the monitoring parameters for Zepatier?

A

transient increase in ALT around week 8
avoid in decompensated cirrhosis

75
Q

What are the drugs in Epclusa?

A

sofosbuvir & velpatasvir
-pan genomic (some exceptions with g3)
=may be a possibility to no longer need to genotype (except g3)

76
Q

What is the cure rate of Epclusa?

A

99-100% cure rate

77
Q

What is an important drug interaction of Epclusa?

A

acid suppressing drugs

78
Q

What are the drugs in Maviret?

A

glecaprevir + pibrentasvir
-all genotypes
-may be used in severe kidney failure and pts who receive a Hep C kidney transplant

79
Q

How should Maviret be taken?

A

with food

80
Q

What are in the drugs in Vosevi?

A

sofosbuvir + velpatasvir + voxilaprevir
-all genotypes

81
Q

What is the role of Vosevi?

A

treatment failure

82
Q

How should Vosevi be taken?

A

with food

83
Q

When should Vosevi be avoided?

A

decompensated cirrhosis

84
Q

Which antivirals are most commonly used for hepatitis C?

A

Epclusa & Maviret

85
Q

What is the estimated percentage of patients living with HCV in Canada that are undiagnosed?

A

40-45%

86
Q

What are the recommendations for hepatitis C testing?

A

population-based screening
-those born between 1945-1975
-CDC says everyone over 18 at least once and pregnancy
risk-based screening
-PWID
-incarceration
-remote blood transfusions
-immigrants from endemic countries

87
Q

What kind of virus is hepatitis D?

A

RNA virus
-occurs simultaneously with HBV

88
Q

How is hepatitis D transmitted?

A

perinatal, blood, sexual

89
Q

Is there a vaccine for hepatitis D?

A

no but hepatitis B vaccine protects

90
Q

What is the sequelae of hepatitis D?

A

chronic disease
cirrhosis
cirrhosis

91
Q

What is the treatment for hepatitis D?

A

PEG INF x 12 months (minimum)

92
Q

What kind of virus is hepatitis E?

A

RNA virus

93
Q

How is hepatitis E transmitted?

A

fecal-oral

94
Q

True or false: there is no vaccine for hepatitis E

A

true

95
Q

What is the sequelae of hepatitis E?

A

high mortality for pregnant women
otherwise patients fare well

96
Q

Describe general prevention for hepatitis viruses.

A

general:
-risk reduction
-education
-active immunization (vaccines)
-passive immunization (immune globulins)
hepatitis A and E:
-good sanitation and hygiene
hepatitis B, C, D:
-universal precautions in institutions
-screening blood

97
Q

Describe general lifestyle considerations for hepatitis C patients.

A

all household members & sexual contacts should be vaccinated (Hep B) and anti-Hb levels tested
abstain from alcohol, tobacco, cannabis
acetaminophen <2g/d for pain, avoid NSAIDs
can share food & utensils, NOT toothbrush, razors, etc
cover all cuts and scrapes
achieve IBW

PHAR255 (24 decks)

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