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Therapeutics > Viral Hepatitis > Flashcards

Viral Hepatitis Flashcards

1
Q

what are the signs and symptoms of acute/chronic hepatitis?

A

nausea/vomiting
anorexia
jaundice
fatigue/malaise

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2
Q

what abnormal lab values will you see in acute/chronic hepatitis?

A 
increased AST/ALT
increased ALk Phos
Increased total bilirubin
Increased INR
decreased albumin
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3
Q

what defines chronic hepatitis?

A

an infection that lasts greater than 6 months

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4
Q

who should be screened for hepatitis B infection?

A
  • people from high-intermediate areas: asia, africa, middle east, European mediterranean, south and central america, eastern europe, caribbean
  • household or sexual contacts of hbv+ persons
  • injection drug users
  • high risk or multiple sexual partners
  • inmates of correctional facilities
  • hepatitis C or HIV infected persons
  • hemodialysis patients
  • pregnant women
  • infants born to HBsAg-Positive mothers
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5
Q

how can hepatitis B be transmitted?

A
  • fluids: blood semen
  • mother to baby
  • transfusion: blood, blood products
  • contaminated needles
  • organ and tissue transplantation
  • close contact to contact
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6
Q

what can you give someone if they aren’t vaccinated against hepatitis B and they are post-exposure?

A
  1. Hepatitis B immune globulin (HBIG)

2. vaccinate against hepatitis B

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7
Q

who should receive the hepatitis B immune globulin?

A
  • infants of HBsAg-positive mothers within 12 hours of birth
  • needlestick within 24 hours if possible, up to 7 days
  • sexual exposure within 14 days
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8
Q

what is the vaccination schedule for hepatitis A vaccine (Havrix, VAQTA)?

A

Month 0 and month 6

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9
Q

what is the vaccination schedule for hepatitis B vaccine (Engerix B, recombivax HB)

A

Month 0, month 1, month 6

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10
Q

what is the vaccinate schedule for hepatitis A/B vaccine (twinrix)

A

Month 0, Month 1, Month 6

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11
Q

what does the HBsAg positive mean?

A

it means you have an active infection. If longer than 6 weeks positive, then you are chronically infected

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12
Q

what does HBeAG positive mean?

A

that there is viral replication going on.

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13
Q

what does HBV DNA positive mean?

A

active infection

viral replication

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14
Q

what does anti-HBs positive mean?

A

it means you have antibodies to hepatitis B surface antigen, leading to immunity to infection.

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15
Q

what does anti-HBe positive mean?

A

it means you have resolution of infection because you have antibodies to hepatitis B “e” antigen.

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16
Q

what does anti-HBc positive mean?

A

prior infection or active infection.

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17
Q

what are your goals for treating hepatitis B with antivirals?

A
  1. prevent cirrhosis, hepatic failure and Hepatocellular carcinoma (HCC)
  2. normalization of liver function test ALT
  3. viral suppression : undetectable HBV DNA, HBeAg seroconversion to anti-HBe, loss of HBsAg
  4. improve liver histology
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18
Q

who should you treat with antiviral therapy for Hepatitis B?

A
  1. people with elevated HBV DNA levels
    a. if HBeAg (+): greater than 20,000IU/ml or greater than 10^5 copies/ml
    b. if HBeAG (-): greater than 2,000IU/ml or greater than 10^4 copies/ml
    ————–AND———
  2. persistently elevated ALT levels >2x ULN.
    a. normal ALT men: 30IU/mL
    b. normal ALT women: 19IU/mL
    OR
  3. moderate/advance liver disease on biopsy: stage 2, 3, or 4 fibrosis
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19
Q

what is the first line antiviral agent for hepatitis B?

A
  1. entecavir (ETV, Baraclude)**
  2. tenofovir
  3. peginterferon
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20
Q

what is the second line oral antiviral agents for hepatitis B?

A

telbivudine (TBV, Tyzeka)

adefovir (ADV, Hepsera)

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21
Q

what is the interferon based injectible preparation that can be used for chronic HBV infection?

A

Pegasys

peginterferon alfa-2a

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22
Q

what is the dosing regimen for pegasys?

A

peginterferon alfa-2a

180 mcg SQ q week x 48 weeks

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23
Q

who should get the best response from pegasys?

A

those with high Alt >100 and relatively low HBV DNA <10^7 copies/mL

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24
Q

what are the adverse effects of pegasys?

A

poorly tolerated
flu-like symptoms: fever, chills, tachycardia, HA
CNS: fatigue, dizziness, depression
Hematologic: neutropenia, leukopenia, anemia
muscular: myalgia, weakness, skeletal pain

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25
Q

what is pegasys contraindicated?

A

liver failure

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26
Q

what is the advantage of pegasys?

A

no emergence of resistance

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27
Q

what are the advantages of tenofovir (TDF, Viread)?

A
  • activity against wild-type and LAM-resistant HBV

- Pregnancy category B

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28
Q

what is the dosing of tenofovir?

A

300mg po qd
ClCr 30-49 ml/min: 300mg po q 48h
ClCr 10-29 ml/min: 300mg po q 72-96hrs

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29
Q

what are the side effects of tenofovir?

A 
CNS: pain, depression
Dermatologic: rash
Metabolic: inc triglycerides
GI: diarrhea, nausea
Renal: nephrotoxicity
Rare: lactic acidosis and hepatic steatosis with nucleoside analogues (maily w/ hiv meds)
30
Q

what are the advantages of entecavir in Hepatits B infection?

A
  • active against wild-type and LAM-resistant HBV
  • Reduces HBV DNA levels by 5-6.9 logs
  • also has activity against HIV
31
Q

what are the disadvantages of entecavir in hepatitis B infection?

A

by year 5, 1.2% of treatment naive patients develop resistance
43% in LAM-resistant patietns

32
Q

what do you do if you get resistance to entecavir? which options do you have?

A
  1. switch to tenofovir
  2. add tenofovir
  3. switch to emtricitabine/tenofovir
33
Q

what is the dose of entecavir?

A
  1. Tretmt naive: 0.5mg po qd
  2. LAM-resistant: 1mg po qd
    ClCr: 30-49 mL/min: 50% of usual dose daily or administer normal dose q48h
    ClCr: 10-29: 30% of usual dose daily or administer the normal dose q72h
34
Q

what are the adverse effects of entecavir?

A

CV: peripheral edma, headache, fatigue
CNS: pyrexia
GI: diarrhea/nausea
Rare: lactic acidosis and hepatic steatosis with nucleoside analogues (mainly HIV meds)

35
Q

what agents exist to treat HBV infection ?

A 
entecavir
tenofovir
adefovir
lamivudine
telbivudine
pegasys
36
Q

how much does lamivudine decrease HBV DNA levels?

A

greater than 5 logs

37
Q

what are the percentages of resistance to lamivudine ?

A

year 1: 24%

year 5: 70%

38
Q

what do you do if you have lamivudine resistance?

A
  1. continue lamivudine and add tenofovir

2. swtich to emtricitabine/tenofovir

39
Q

what is the dose of lamivudine?

A
  1. 100mg po daily
  2. For HIV coinfection: 150mg po BID
    ClCr 30-49 ml/min: 100mg first dose, then 50mg po daily
    ClCr 15-29 ml/min: 100mg first dose, then 25mg po daily
    ClCr 5-14 ml/min: 35mg first dose, then 15mg po daily
    ClCr <5ml/min: 35mg first dose, then 10mg po daily
40
Q

what are the adverse effects of lamivudine?

A

CNS: HA, fatigue, insomnia
GI: diarrhea/nausea, pancreatitis, abdominal pain
Hematologic: neutropenia
Muscular: myalgia, neuropathy, musculoskeletal pain
Rare: lactic acidosis and hepatic steatosis with nucleoside analogues (mainly w/ HIV meds)

41
Q

what are the advantages of adefovir (Hepsera)

A
  • activity agains wild-type and LAM-resistant HBV

- Reduces HBV DNA levels by 3.6-4.5 logs

42
Q

what are the disadvantages of adefovir?

A

-not as potent at tenofovir, lamivudine, entecavir, telbivudine

43
Q

what are the resistance levels of adefovir?

A

28% by year 5

44
Q

what do you do if you get resistance to adefovir?

A
  1. switch to entecavir
  2. add entecavir (if no LAM-resistance)
  3. switch to emtricitabine/tenfovir
45
Q

what is the dose of adefovir?

A

10mg po qd
ClCr 20-49ml/min: 10mg po q48h
ClCr 10-19ml/min: 10mg po q72h

46
Q

what are the adverse effects of adefovir?

A 
CNS: headache
GI: abdominal pain
hematologic: neutropenia
Muscular: weakness
Renal: nephrotoxicity
rare: lactic acidosis and hepatic steatosis with nucleoside analogues (mainly w/ hiv meds)
47
Q

what are the advantages of Telbivudine (TBV, Tyzeka)?

A
  • lowers HBV DNA levels by 6 logs
  • less resistance compared to lamivudine
  • pregnancy category B
48
Q

what are the levels of resistance for telbivudine?

A

HBeAG (+): yr 1-4.4%, yr 2-21.6%

HBeAG (-): yr 1-2.7%, yr 2-8.6%

49
Q

what is the dose of telbivudine?

A

600mg po qd
ClCr 30-49ml/min: 600mg po q48
ClCr <30 ml/min: 600mg po q72h

50
Q

what are the adverse effects of telbivudine?

A

similar to lamivudine

51
Q

what are the advantages of emtricitabine (FTC, emtriva)?

A

-also has activity against HIV

52
Q

what is the dose of emtricitabine?

A

for HIV 200mg po qd

dose adjustment for ClCr <50ml/min

53
Q

what are the adverse effects of emtricitabine?

A

similar to lamivudine

54
Q

when is tenofovir indicated?

A

as first line treatment

in the case of lamivudine, entecavir, or adefovir resistance

55
Q

when is entecavir indicated?

A

first line option

adefovir resistance

56
Q

how long should treatment be for hepatitis B infection?

A

at least 12 months

57
Q

when should you consider discontinuing antiviral therapy?

A

when you get HBsAG seroconversion on 2 separate occasions, at 6-12 months apart.

58
Q

what patient counseling can you give for hepatitis B infection?

A
  1. Avoid Alcohol
  2. Avoid hepatotoxins inc: acetamiophen >2g/day
  3. consult HCP before beginning new meds like herbal remedies
  4. do not share needles, toothbrushes, razors
  5. cover open cuts/sores
  6. adopt safe sex practices
  7. check immunity of household members and sexual partners, vaccinate if needed
59
Q

how is hepatitis C virus transmitted?

A 
through the skin
-injection drug use
-blood transfusion or organ transplant before 1992
-use of clotting factors before 1987
-occupational exposure (needlestick)
Permucosal
-mother to child
-sexual
60
Q

who should have risk factor screening for HCV ?

A

all patients

61
Q

who should receive the HCV antibody test?

A

patient with risk factors

patients who request testing

62
Q

who should receive the HCV-RNA qualitative or quatitative test?

A

patients who tested positive for HCV antibody

63
Q

who should receive the HCV-RNA (quantitative) test?

A

patients whom treatment is to be initiated or who are on treatment to assess response to therapy

64
Q

what are your treatment goals for Hep C antiviral tx?

A
  • improve survival
  • eradicate virus
    a. Achieve sustained virologic response(SVR): Undetectable HCV RNA, 6 months post-treatment
  • improve liver histology
  • reduce risk of heptocellular carcinoma
  • reduce need for liver transplantation
65
Q

what are the adverse effects of boceprivir-PEG-ribavirin?

A
  • anemia
  • neutropenia
  • altered taste
66
Q

what are the adverse effects of telaprevir-PEG-ribavirin?

A
  • rash, pruritis
  • anemia
  • GI upset
  • altered taste
  • inc uric acid levels
  • increased total bilirubin
  • anorectal symptoms
67
Q

what are the adverse effects of PEG-ribavirin?

A
  • flu-like symptoms
  • bone marrow suppression
  • mental helath
  • GI upset
  • Rash
  • Thyroid, DM retinopathy
68
Q

what is the patient counseling for patients with HCV infection?

A

same as Hep B V plus

Avoide high doses of fat soluble vitamins

69
Q

who should receive HCV antiviral treatment?

A
  • detectable levels of HCV RNA
  • > 18 yo
  • sigficant fibrosis liver biopsy stage 2 or greater fibrosis
  • compensated liver disease
  • acceptable hematological and biochemical indices
  • willing to adhere
  • no contraindications
70
Q

what are contraindications for PEG-Ribavirin treatment?

A

-uncontrolled mental illness
-solid organ transplant (renal, heart, lung)
-Autoimmune hepatitis or other autoimmune conditions
- Untreated thyroid disease or diabetes mellitus
- Pregnant or unwilling to comply with contraception
- Severe concurrent medical
disease
- end stage AIDS, cancer

71
Q

what dosing should you use for peginteferon-rivabirin?

A
  1. Peginterferon alfa-2a 180mcg sq q week
    CrCl < 30ml/min or hemodialysis: 135mcg sq q week
    OR
    Peginterferon alfa-2b 1.5mcg/kg sq q week
    CrCL =75kg) or alternative dosing (see slides) Dose adjust for CrCl <50ml/min TREAT for 48 weeks
    OR
    GENOTYPE 2 or 3: rivabirin 800mg/day (2 divided doses) )

Therapeutics (23 decks)

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