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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
How long is hepatitis B therapy with interferons?
16-48 week course -30% successful in developing immunity
26
What are the advantages of interferons?
shorter course of therapy absence of resistance a chance at full seroconversion
27
In which patients are interferons used?
patients with lower HBV DNA levels and elevated aminotransferase values
28
What are the disadvantages of interferons?
CI in decompensated cirrhosis -increased risk of life-threatening infections and worsening hepatic dysfunction SC injection many side effects
29
What is the response rate with nucleoside analogues?
> 90% response -10-15% success in developing immunity
30
What are the advantages of nucleoside analogues?
safer fewer side effects oral
31
What are the disadvantages of nucleoside analogues?
chronic therapy -endpoint: seroconversion in 12 months -can take years, indefinite therapy in some drug resistance adjust in renal dysfunction
32
What is the MOA of lamivudine?
pyrimidine nucleoside analogue inhibitor of HBV
33
What was the first oral agent approved for hepatitis B?
lamivudine
34
What is the safety and efficacy of lamivudine?
well tolerated and effective but resistance rates approaching 70% at 4 years -no longer DOC for hep B
35
What is the main use of lamivudine?
prophylaxis (hep B) for those on immunosuppression pregnant women
36
What is the MOA of adefovir?
nucleotide analogue
37
What is the efficacy of adefovir?
less potent & does not achieve viral suppression in most in the first year -not the DOC for hep B
38
What is the use of adefovir?
add on in lamivudine resistance
39
What are the side effects of adefovir?
nephrotoxicity hypophosphatemia
40
What is the DOC for hepatitis B?
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
How many salts are there for tenofovir?
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
What is the MOA of tenofovir?
purine nucleotide reverse transcriptase inhibitor
43
Which hepatitis B drug is the most potent and has the lowest chance of resistance?
tenofovir
44
What is the MOA of entecavir?
selective guanisine analogue and potent inhibitor of HBV DNA replication
45
When is combo therapy used for hepatitis B?
people with cirrhosis who have resistance -may have a fatal flare *add on approach*
46
What kind of virus is hepatitis C?
single-stranded RNA virus
47
How is hepatitis C transmitted?
perinatal, sexual, blood -parenteral most effective -sexual transmission very low
48
True or false: there is a vaccine available for hepatitis C
false
49
What are the symptoms of hepatitis C?
70% of patients are asymptomatic if symptoms occur: -jaundice -dark urine -white stool -abdominal pain -fatigue -fever -loss of appetite -pruritis
50
What is the sequelae of hepatitis C?
chronic disease (75%; 25% spontaneously resolve) cirrhosis hepatocellular carcinoma
51
How long could it take for the first clinical presentation of hepatitis C?
20-30y post exposure
52
Which hepatitis C genotypes are most common in Canada?
1a, 1b, 2, 3 *there are many different genotypes of hepatitis C*
53
What are the serological marker for hepatitis C?
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
What was the traditional primary objective for hepatitis C treatment? What is the objective today?
traditionally: -complete elimination of virus as undetectable HCV RNA at least 24-48wks post-treatment today: -8 to 12 weeks
55
What was the traditional treatment of hepatitis C?
interferon and ribavirin combo -treatment has since evolved
56
What is the MOA of ribavirin?
nucleoside analogue
57
What is the dosing frequency of ribavirin?
po BID
58
What is the antiviral spectrum of ribavirin?
very broad spectrum -DNA, RNA, influenza, flavaviruses, viral hemorrhagic fevers
59
What are the side effects of ribavirin?
hemolytic anemia, rash, depression, fatigue, insomnia *teratogen: male & female (contraception x 6mo post-tx)
60
What is the tolerability of ribavirin + IFN?
nasty side effects
61
Which genotype of hepatitis C does simeprevir target?
genotype 1
62
What is the dosing and side effects of simeprevir?
OD dosing with food AE: rash, pruritis, nausea, photosensitivity
63
What is the problem with simeprevir?
resistance
64
What is the efficacy of sofosbuvir?
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
What is the treatment duration with sofosbuvir?
12-24 wks (depending on strain)
66
What are the drug interactions of sofosbuvir?
substrate of P-gp -induces may decrease levels bradycardia when given with amiodarone
67
What are the benefits of sofosbuvir?
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
What are the cons of sofosbuvir?
accumulates in renal disease not great results in g3
69
Which drugs are in Harvoni?
ledipasvir & sofosbuvir
70
What is an important drug interaction of Harvoni?
co-administration with PPIs -decreased absorption
71
What are the side effects of Harvoni?
*mild to moderate in severity* fatigue headache insomnia nausea
72
What are the drugs in Zepatier?
grazoprevir & elbasavir
73
Which patient population has Zepatier been studied in?
difficult to treat or lack of data in literature (PWID, renal)
74
What are the monitoring parameters for Zepatier?
transient increase in ALT around week 8 *avoid in decompensated cirrhosis*
75
What are the drugs in Epclusa?
sofosbuvir & velpatasvir -pan genomic (some exceptions with g3) =may be a possibility to no longer need to genotype (except g3)
76
What is the cure rate of Epclusa?
99-100% cure rate
77
What is an important drug interaction of Epclusa?
acid suppressing drugs
78
What are the drugs in Maviret?
glecaprevir + pibrentasvir -all genotypes -may be used in severe kidney failure and pts who receive a Hep C kidney transplant
79
How should Maviret be taken?
with food
80
What are in the drugs in Vosevi?
sofosbuvir + velpatasvir + voxilaprevir -all genotypes
81
What is the role of Vosevi?
treatment failure
82
How should Vosevi be taken?
with food
83
When should Vosevi be avoided?
decompensated cirrhosis
84
Which antivirals are most commonly used for hepatitis C?
Epclusa & Maviret
85
What is the estimated percentage of patients living with HCV in Canada that are undiagnosed?
40-45%
86
What are the recommendations for hepatitis C testing?
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
What kind of virus is hepatitis D?
RNA virus -occurs simultaneously with HBV
88
How is hepatitis D transmitted?
perinatal, blood, sexual
89
Is there a vaccine for hepatitis D?
no but hepatitis B vaccine protects
90
What is the sequelae of hepatitis D?
chronic disease cirrhosis cirrhosis
91
What is the treatment for hepatitis D?
PEG INF x 12 months (minimum)
92
What kind of virus is hepatitis E?
RNA virus
93
How is hepatitis E transmitted?
fecal-oral
94
True or false: there is no vaccine for hepatitis E
true
95
What is the sequelae of hepatitis E?
high mortality for pregnant women otherwise patients fare well
96
Describe general prevention for hepatitis viruses.
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
Describe general lifestyle considerations for hepatitis C patients.
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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