Viral Hepatitis Flashcards
1
Q
what are the signs and symptoms of acute/chronic hepatitis?
A
nausea/vomiting
anorexia
jaundice
fatigue/malaise
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
3
Q
what defines chronic hepatitis?
A
an infection that lasts greater than 6 months
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
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
6
Q
what can you give someone if they aren’t vaccinated against hepatitis B and they are post-exposure?
A
- Hepatitis B immune globulin (HBIG)
2. vaccinate against hepatitis B
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
8
Q
what is the vaccination schedule for hepatitis A vaccine (Havrix, VAQTA)?
A
Month 0 and month 6
9
Q
what is the vaccination schedule for hepatitis B vaccine (Engerix B, recombivax HB)
A
Month 0, month 1, month 6
10
Q
what is the vaccinate schedule for hepatitis A/B vaccine (twinrix)
A
Month 0, Month 1, Month 6
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
12
Q
what does HBeAG positive mean?
A
that there is viral replication going on.
13
Q
what does HBV DNA positive mean?
A
active infection
viral replication
14
Q
what does anti-HBs positive mean?
A
it means you have antibodies to hepatitis B surface antigen, leading to immunity to infection.
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.
16
Q
what does anti-HBc positive mean?
A
prior infection or active infection.
17
Q
what are your goals for treating hepatitis B with antivirals?
A
- prevent cirrhosis, hepatic failure and Hepatocellular carcinoma (HCC)
- normalization of liver function test ALT
- viral suppression : undetectable HBV DNA, HBeAg seroconversion to anti-HBe, loss of HBsAg
- improve liver histology
18
Q
who should you treat with antiviral therapy for Hepatitis B?
A
- 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——— - persistently elevated ALT levels >2x ULN.
a. normal ALT men: 30IU/mL
b. normal ALT women: 19IU/mL
OR - moderate/advance liver disease on biopsy: stage 2, 3, or 4 fibrosis
19
Q
what is the first line antiviral agent for hepatitis B?
A
- entecavir (ETV, Baraclude)**
- tenofovir
- peginterferon
20
Q
what is the second line oral antiviral agents for hepatitis B?
A
telbivudine (TBV, Tyzeka)
adefovir (ADV, Hepsera)
21
Q
what is the interferon based injectible preparation that can be used for chronic HBV infection?
A
Pegasys
peginterferon alfa-2a
22
Q
what is the dosing regimen for pegasys?
A
peginterferon alfa-2a
180 mcg SQ q week x 48 weeks
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
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
25
what is pegasys contraindicated?
liver failure
26
what is the advantage of pegasys?
no emergence of resistance
27
what are the advantages of tenofovir (TDF, Viread)?
- activity against wild-type and LAM-resistant HBV
| - Pregnancy category B
28
what is the dosing of tenofovir?
300mg po qd
ClCr 30-49 ml/min: 300mg po q 48h
ClCr 10-29 ml/min: 300mg po q 72-96hrs
29
what are the side effects of tenofovir?
```
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
what are the advantages of entecavir in Hepatits B infection?
- active against wild-type and LAM-resistant HBV
- Reduces HBV DNA levels by 5-6.9 logs
- also has activity against HIV
31
what are the disadvantages of entecavir in hepatitis B infection?
by year 5, 1.2% of treatment naive patients develop resistance
43% in LAM-resistant patietns
32
what do you do if you get resistance to entecavir? which options do you have?
1. switch to tenofovir
2. add tenofovir
3. switch to emtricitabine/tenofovir
33
what is the dose of entecavir?
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
what are the adverse effects of entecavir?
CV: peripheral edma, headache, fatigue
CNS: pyrexia
GI: diarrhea/nausea
Rare: lactic acidosis and hepatic steatosis with nucleoside analogues (mainly HIV meds)
35
what agents exist to treat HBV infection ?
```
entecavir
tenofovir
adefovir
lamivudine
telbivudine
pegasys
```
36
how much does lamivudine decrease HBV DNA levels?
greater than 5 logs
37
what are the percentages of resistance to lamivudine ?
year 1: 24%
| year 5: 70%
38
what do you do if you have lamivudine resistance?
1. continue lamivudine and add tenofovir
| 2. swtich to emtricitabine/tenofovir
39
what is the dose of lamivudine?
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
what are the adverse effects of lamivudine?
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
what are the advantages of adefovir (Hepsera)
- activity agains wild-type and LAM-resistant HBV
| - Reduces HBV DNA levels by 3.6-4.5 logs
42
what are the disadvantages of adefovir?
-not as potent at tenofovir, lamivudine, entecavir, telbivudine
43
what are the resistance levels of adefovir?
28% by year 5
44
what do you do if you get resistance to adefovir?
1. switch to entecavir
2. add entecavir (if no LAM-resistance)
3. switch to emtricitabine/tenfovir
45
what is the dose of adefovir?
10mg po qd
ClCr 20-49ml/min: 10mg po q48h
ClCr 10-19ml/min: 10mg po q72h
46
what are the adverse effects of adefovir?
```
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
what are the advantages of Telbivudine (TBV, Tyzeka)?
- lowers HBV DNA levels by 6 logs
- less resistance compared to lamivudine
- pregnancy category B
48
what are the levels of resistance for telbivudine?
HBeAG (+): yr 1-4.4%, yr 2-21.6%
| HBeAG (-): yr 1-2.7%, yr 2-8.6%
49
what is the dose of telbivudine?
600mg po qd
ClCr 30-49ml/min: 600mg po q48
ClCr <30 ml/min: 600mg po q72h
50
what are the adverse effects of telbivudine?
similar to lamivudine
51
what are the advantages of emtricitabine (FTC, emtriva)?
-also has activity against HIV
52
what is the dose of emtricitabine?
for HIV 200mg po qd
| dose adjustment for ClCr <50ml/min
53
what are the adverse effects of emtricitabine?
similar to lamivudine
54
when is tenofovir indicated?
as first line treatment
| in the case of lamivudine, entecavir, or adefovir resistance
55
when is entecavir indicated?
first line option
| adefovir resistance
56
how long should treatment be for hepatitis B infection?
at least 12 months
57
when should you consider discontinuing antiviral therapy?
when you get HBsAG seroconversion on 2 separate occasions, at 6-12 months apart.
58
what patient counseling can you give for hepatitis B infection?
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
how is hepatitis C virus transmitted?
```
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
who should have risk factor screening for HCV ?
all patients
61
who should receive the HCV antibody test?
patient with risk factors
| patients who request testing
62
who should receive the HCV-RNA qualitative or quatitative test?
patients who tested positive for HCV antibody
63
who should receive the HCV-RNA (quantitative) test?
patients whom treatment is to be initiated or who are on treatment to assess response to therapy
64
what are your treatment goals for Hep C antiviral tx?
- 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
what are the adverse effects of boceprivir-PEG-ribavirin?
- anemia
- neutropenia
- altered taste
66
what are the adverse effects of telaprevir-PEG-ribavirin?
- rash, pruritis
- anemia
- GI upset
- altered taste
- inc uric acid levels
- increased total bilirubin
- anorectal symptoms
67
what are the adverse effects of PEG-ribavirin?
- flu-like symptoms
- bone marrow suppression
- mental helath
- GI upset
- Rash
- Thyroid, DM retinopathy
68
what is the patient counseling for patients with HCV infection?
same as Hep B V plus
| Avoide high doses of fat soluble vitamins
69
who should receive HCV antiviral treatment?
- 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
what are contraindications for PEG-Ribavirin treatment?
-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
what dosing should you use for peginteferon-rivabirin?
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) )
