Viral Hepatitis Flashcards
what are the signs and symptoms of acute/chronic hepatitis?
nausea/vomiting
anorexia
jaundice
fatigue/malaise
what abnormal lab values will you see in acute/chronic hepatitis?
increased AST/ALT increased ALk Phos Increased total bilirubin Increased INR decreased albumin
what defines chronic hepatitis?
an infection that lasts greater than 6 months
who should be screened for hepatitis B infection?
- 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
how can hepatitis B be transmitted?
- fluids: blood semen
- mother to baby
- transfusion: blood, blood products
- contaminated needles
- organ and tissue transplantation
- close contact to contact
what can you give someone if they aren’t vaccinated against hepatitis B and they are post-exposure?
- Hepatitis B immune globulin (HBIG)
2. vaccinate against hepatitis B
who should receive the hepatitis B immune globulin?
- 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
what is the vaccination schedule for hepatitis A vaccine (Havrix, VAQTA)?
Month 0 and month 6
what is the vaccination schedule for hepatitis B vaccine (Engerix B, recombivax HB)
Month 0, month 1, month 6
what is the vaccinate schedule for hepatitis A/B vaccine (twinrix)
Month 0, Month 1, Month 6
what does the HBsAg positive mean?
it means you have an active infection. If longer than 6 weeks positive, then you are chronically infected
what does HBeAG positive mean?
that there is viral replication going on.
what does HBV DNA positive mean?
active infection
viral replication
what does anti-HBs positive mean?
it means you have antibodies to hepatitis B surface antigen, leading to immunity to infection.
what does anti-HBe positive mean?
it means you have resolution of infection because you have antibodies to hepatitis B “e” antigen.
what does anti-HBc positive mean?
prior infection or active infection.
what are your goals for treating hepatitis B with antivirals?
- 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
who should you treat with antiviral therapy for Hepatitis B?
- 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
what is the first line antiviral agent for hepatitis B?
- entecavir (ETV, Baraclude)**
- tenofovir
- peginterferon
what is the second line oral antiviral agents for hepatitis B?
telbivudine (TBV, Tyzeka)
adefovir (ADV, Hepsera)
what is the interferon based injectible preparation that can be used for chronic HBV infection?
Pegasys
peginterferon alfa-2a
what is the dosing regimen for pegasys?
peginterferon alfa-2a
180 mcg SQ q week x 48 weeks
who should get the best response from pegasys?
those with high Alt >100 and relatively low HBV DNA <10^7 copies/mL
what are the adverse effects of pegasys?
poorly tolerated
flu-like symptoms: fever, chills, tachycardia, HA
CNS: fatigue, dizziness, depression
Hematologic: neutropenia, leukopenia, anemia
muscular: myalgia, weakness, skeletal pain
what is pegasys contraindicated?
liver failure
what is the advantage of pegasys?
no emergence of resistance
what are the advantages of tenofovir (TDF, Viread)?
- activity against wild-type and LAM-resistant HBV
- Pregnancy category B
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
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)
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
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
what do you do if you get resistance to entecavir? which options do you have?
- switch to tenofovir
- add tenofovir
- switch to emtricitabine/tenofovir
what is the dose of entecavir?
- Tretmt naive: 0.5mg po qd
- 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
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)
what agents exist to treat HBV infection ?
entecavir tenofovir adefovir lamivudine telbivudine pegasys
how much does lamivudine decrease HBV DNA levels?
greater than 5 logs
what are the percentages of resistance to lamivudine ?
year 1: 24%
year 5: 70%
what do you do if you have lamivudine resistance?
- continue lamivudine and add tenofovir
2. swtich to emtricitabine/tenofovir
what is the dose of lamivudine?
- 100mg po daily
- 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
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)
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
what are the disadvantages of adefovir?
-not as potent at tenofovir, lamivudine, entecavir, telbivudine
what are the resistance levels of adefovir?
28% by year 5
what do you do if you get resistance to adefovir?
- switch to entecavir
- add entecavir (if no LAM-resistance)
- switch to emtricitabine/tenfovir
what is the dose of adefovir?
10mg po qd
ClCr 20-49ml/min: 10mg po q48h
ClCr 10-19ml/min: 10mg po q72h
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)
what are the advantages of Telbivudine (TBV, Tyzeka)?
- lowers HBV DNA levels by 6 logs
- less resistance compared to lamivudine
- pregnancy category B
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%
what is the dose of telbivudine?
600mg po qd
ClCr 30-49ml/min: 600mg po q48
ClCr <30 ml/min: 600mg po q72h
what are the adverse effects of telbivudine?
similar to lamivudine
what are the advantages of emtricitabine (FTC, emtriva)?
-also has activity against HIV
what is the dose of emtricitabine?
for HIV 200mg po qd
dose adjustment for ClCr <50ml/min
what are the adverse effects of emtricitabine?
similar to lamivudine
when is tenofovir indicated?
as first line treatment
in the case of lamivudine, entecavir, or adefovir resistance
when is entecavir indicated?
first line option
adefovir resistance
how long should treatment be for hepatitis B infection?
at least 12 months
when should you consider discontinuing antiviral therapy?
when you get HBsAG seroconversion on 2 separate occasions, at 6-12 months apart.
what patient counseling can you give for hepatitis B infection?
- Avoid Alcohol
- Avoid hepatotoxins inc: acetamiophen >2g/day
- consult HCP before beginning new meds like herbal remedies
- do not share needles, toothbrushes, razors
- cover open cuts/sores
- adopt safe sex practices
- check immunity of household members and sexual partners, vaccinate if needed
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
who should have risk factor screening for HCV ?
all patients
who should receive the HCV antibody test?
patient with risk factors
patients who request testing
who should receive the HCV-RNA qualitative or quatitative test?
patients who tested positive for HCV antibody
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
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
what are the adverse effects of boceprivir-PEG-ribavirin?
- anemia
- neutropenia
- altered taste
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
what are the adverse effects of PEG-ribavirin?
- flu-like symptoms
- bone marrow suppression
- mental helath
- GI upset
- Rash
- Thyroid, DM retinopathy
what is the patient counseling for patients with HCV infection?
same as Hep B V plus
Avoide high doses of fat soluble vitamins
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
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
what dosing should you use for peginteferon-rivabirin?
- 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) )
