Module 8: Viral Hepatitis Flashcards
Dr. Covert EXAM VI (Final)
How is Hep A (HAV) treated?
Symtoms: N/V, flu-like symtoms
Self-limited
What are the lab signs to diagnose HAV?
-Immunoglobulin M antibody to HAV
-elevation of LFTs
Name the HAV vaccines
KNOW the vaccines
-Pre-Exposure prophylaxis
-HAV: Havrix, Vaqt
-HAV + HBV: Twinrix
Candidates: anyone older than 1; those at risk
MSM, IVDU, Occupational risk of
exposure, Patients with chronic liver disease
Hep B vaccines
-3 dose series
-HBV: Energix-B, Recombivax HB, Pediarix
-HBV + HAV: Twinirix
Candidates:
Infants, Adolescents/ children previously unvaccinated
-IVDU (IV drug use)
-At risk of infection by sexual exposure
-Healthcare workers
-Dialysis patients, Patients with DM
-Patients with HCV
Which of the Hepatitis types require 3 dose series?
Hep B
All HCV patients should receive HAV and HBV vaccines. T/F
True
There is no Hep C vaccine -> it heavily damages the liver, HBV and HAV vaccines to prevent other liver infections
What should be considered in patients with chronic liver diseases?
Pneumococcal vaccination PPSV23
1st dose at diagnosis
2nd dose at 65 yo (if > 5y from 1st dose)
Can HBV transmitted from perinatal (from mom to baby)?
Yes
other ways
-sex with an infected partner
-injection drug use
-contact with blood
-needle sticks
When is HBV considered chronic?
detectable surface antigen 6 months after initial infection
Signs and symptoms:
-Jaundice!
-Fever
-Fatigue
-N/V, abdominal pain, decreased appetite
Which antigen is detected first in the acute phase of an HBV infection?
Surace antigen HBsAg
-remains detectable in chronic infections
-gives information about the presence or absence of HBV
Which antigen gives information about the ongoing replication of HBV?
E antigen HBeAg
When should antiviral treatment for an HBV infection be considered?
if the infection becomes chronic (no cure, life-long treatment) -> not all chronic patients get treatment though
-no treatment available for the acute phase
Factors that determine HBV treatment or no treatment
-Age (if too old, probably die due to other conditions)
-HBV DNA load (also HBeAg)
-ALT levels
-disease progression
*not all chronic HBV patients are candidates for treatment
Guideline to decide on HBV antiviral treatment
E-antigen positive
- HBsAg positive? -> always (+) in chronic patients
- HBeAg positive? -> Yes
- ALT >2XULN (ALT is an early sign of cytotoxic injury of the liver)
- treat if HBV DNA is > 20.000 IU/ml
if ALT < ULN. Do not treat. monitor ALT and HBV DNA every 3-6 months and HBeAg every 6-12 months
When to initiate treatment for HBV in patients who are E-antigen negative?
-the virus replicates slower
-positive for HBsAg and HBeAg
-ALT > 2XULN
-HBV DNA > 2000 IU/ml
Do not treat if: ALT > ULN and HBV DNA < 2000 IU/ml and monitor ALT and HBV DNA for 3-6 months, HBsAg annually
Pharmacologic Treatment
-Entecavir ETV (Baraclude)
-Tenofovir dipovoxil fumarate TDF (Viread)
-Tenofovir alafenamide TAF (vemlidy)
Interferons: often used when ETV/TDF/TAF failed
-Interferon alfa-2b (Intron A)
-Peginterferon alfa-2b (pegasys)
What is the first-line treatment for HBV?
Interferons (Entecavir and tenofovir are also 1st line)
-MOA: enhances host immune system
-INF alfa-2b: 5 million IU SQ daily or 10 million IU 3x weekly X 16-24 weeks
-Peg-INF: 180 mcg SQ once weekly X 48 weeks
Peg-INF (same as INF-alfa2b) is more lost-lasting
What are the ADE for Interferons?
-flu-like symptoms
-suicidal ideation
-depression
-anxiety
-anemia
-GI intolerance
-bone marrow suppression
Contraindication for Interferons
KNOW when NOT to prescribe
-current psychosis
-severe depression
-neutropenia
-thrombocytopenia
-seizures
-decompensated liver disease
-symptomatic heart disease
MOA and dose of Entecavir
-Guanosine nucleoside analog: inhibits HBV replication at 3 steps
-0.5-1 mg PO daily (don’t need to know)
-more potent than adefovir or lamivudine with minimal resistance
ADR: headache, cough, abdominal pain
MOA and dose of Tenofovir
-Nucleotide analog: inhibits DNA polymerase
-highly potent, minimal resistant
-ADR: nephrotoxicity with TDF
-TDF IS preferred in pregnancy
-co-formulated in several HIV regimens
*Complera, Genvoya, Descovy, Odefsey
What prophylactic interventions for HCV?
There is no vaccine
-patients should get HBV and HAV vaccine
HCV Symptoms
-Jaundice
-dark urine!
-fatigue
-fever
-abdominal pain, N/V
-poor appetite
-weakness
Which patients should be considered for HCV treatment?
-all patients with chronic HCV
Exception: Short-life expectancies secondary to comorbidities
Meaning of SVS
Sustained viral response (SVR) = virologic cure
-presence of HCV antibodies
-absence of detectable HCV RNA 12 weeks after antiviral therapy
Suffixes for HCV antivirals
Protease inhibitors (pr):
-Grazoprevir, Glecaprevir, Voxilaprevir
NS5A inhibitor (asvir)
-Ledipasvir, Pibrentasvir, Velpatasvir
NS5B inhibitor (busvir)
-Sofosbuvir, Dasabuvir
MOA of HCV antivirals
Protease inhibitors (pr):
-inhibits the enzyme that cleaves NS4B + NS5A (replication complex), NS5B
NS5A inhibitor (asvir)
-replication complex (NS4B + NS5A) cant form
NS5B inhibitor (busvir)
-NS5B = polymerase complex, blocks the complex
Harvoni
Sofosbuvir/Ledipasvir
DDI: amiodarone (Sofosbuvir) and antiacids (Ledipasvir)
Epclusa
Sofosbuvir/ Velpatasvir
DDI: amiodarone (Sofosbuvir) and antiacids (Velpatasvir)
Vosevi
Sofosbuvir/ Velpatasvir/ Voxilaprevir
Zepatier
Elbasvir/ Grazoprevir
Mavyret
Glecaprevir/ Pibrentasvir
Which HCV antiviral causes symptomatic bradycardia when taken with amiodarone?
Sofosbuvir (NS5B inhibitor)
*Harvoni
*Epclusa
*Vosevi
Which HCV antiviral has a DDI with PPIs?
Velpatasvir (decreased absorption)
*Epclusa
*Vosevi
with antiacids:
Ledipasvir (decreased absorption)
*Harvoni
Which HCV may increase LFTs and can be used in ESRD-HD patients?
Elbasvir/Grazoprevir (Zepatier)
Which HCV antiviral can be used for all genotypes?
!!!
Glecaprevir/ Pibrentasvir (Mavyret)
(+) first 8-week treatment option (the others ones are at least 12 weeks)
(+) all genotypes
(+) option for a simplified regimen
(-) contraindicated: Child-Pugh C, rifampin, atazanavir
(-) DDIs -> reduce concentration of: statins, carbamazepine, cyclosporine, ethinyl estradiol (oral contraceptives)
Which other antiviral covers all genotypes?
Sofosbuvir/ Velpatasvir (Epclusa)
(+) option for a simplified regimen
(+) all genotypes
Sofosbuvir/ Velpatasvir/ Voxilaprevir (Vosevi)
(+) all genotypes
What are common ADEs in HCV antivirals?
-Fatigue
-h/a
-nausea
-diarrhea
What is the role of Ribavirin in HCV therapy?
-for patients who developed HCV drug resistance
-severe cirrhosis (as a result of the resistance)
-BBW: not effective alone, combined with other oral HCV antivirals!
-contraindicated in pregnancy, lots of side effects
Simplified treatment
-can be started after treatment: other need to determine genotypes and resistance
Mavyret X 8 weeks
Epclusa X 12 weeks
patients should not have:
End-stage renal disease (only with Zepatier)
HIV
history of HCV treatment (may have resistance to Mavyret or Epclusa)
pregnancy
prior liver transplant
cirrhosis
Which of the antivirals offering simplified treatment has a DDI with carbamazepine, cyclosporine, statins, and oral contraceptives?
Mavyret (Glecaprevir/ Pibrentasvir)
change to Epclusa: Sofosbuvir/ Velpatasvir
-> DDI with amiodarone and antacids (PPIs)
Which HCV antiviral combo is similar to Epclusa but does not cover all genotypes?
Harvoni (Sofosbuvir/Ledipasvir)
DDI: amiodarone (Sofosbuvir) and antiacids (Ledipasvir)
