Viral Hepatitis Flashcards
T or F: HBV is an RNA virus
FALSE
RNA viruses – except HBV (which is a DNA virus)
HBV and HCV can also produce a ___ infection
chronic
___ : fecal-oral
- direct contact
___ : blood, sexual
- born to infected mother
- chronic, not curative
___ : blood
- IV drug use
- chronic, curative
- no protective immunity or vaccine available
HAV, HBV, HCV
Diagnosis & Serologic Testing
Diagnosis of acute HAV requires the detection of either:
- ___ anti-HAV in serum (usually becomes detectable within 5-10 days of symptom onset) OR
- HAV ___ in serum or stool
___ anti-HAV appears early in the infection, remains detectable providing lifelong immunity
- Total anti-HAV (measuring both IgG and IgM) is used to assess ___
- IgM
- IgG
- RNA
- immunity
HAV management
Supportive care
- No role of antiviral agents for treatment
Vaccine available
- Two dose series given at 0 and 6-12 months
- Inactivated vaccine – safe in pregnancy
- Pre- and post-vaccination serologic screening is typically not recommended
- Post-exposure ___ should be given ASAP after exposure (within 2 weeks)
prophylaxis
HBV Transmission
Percutaneous or mucosal contact
- Sexual contact
- Injecting drug use
- Mother-to-child transmission
- Contact with blood or open sores
- Needle sticks
- Sharing razors or toothbrushes
CANNOT be spread by
* Food
* Water
* Sharing eating utensils
* Breastfeeding
* Kissing
* Coughing
* Sneezing
* Holding hands
HBV Screening Recommendations
- triple panel test
- Screen for ___ during each pregnancy
- People who are at ongoing risk for exposure should be tested periodically
HBsAg
HBV Serologic Markers: triple panel
- HBsAg: Is the patient infectious?
- anti-HBs: is the patient immune?
- Total anti-HBc: Has the patient been exposed to the virus?
anti-HBs: we dont know if they acquired immunity from virus or vaccine tho
core: vaccine doesnt have core
HBV Serologic Markers: triple panel
- Susceptible, never infected (if no documentation of HepB vaccine series completion)
- give vaccine
HBV Serologic Markers: triple panel
Resolved infection
- Counsel about HBV infection reactivation risk
HBV Serologic Markers: triple panel
- immune from vaccine
- If not vaccinated, then complete vaccine series
HBV Serologic Markers: triple panel
acute infection
- Link to hepatitis B care
HBV Serologic Markers: triple panel
Chronic infection
Link to hepatitis B care
HBV Management - Chronic Infection
Initial evaluation
* History (risk factors) and physical exam
* CBC, ___ panel, INR, ___, anti-HBe, HBV DNA ___
- liver, HBeAg, PCR
Principles of Treatment
ALT upper limit of normal (ULN) is ___ U/L for males and ___ U/L for females
For most, duration of nucleoside analog (NA) therapy is ___
Treatment Eligibility
- HBV DNA > ___ IU/mL (> 10,000 copies/mL)
- weird exception for e+ immune active ( > ___ IU/mL)
- ALT > 2xULN; or Cirrhosis
35, 25
indefinite
2,000
20,000
HBV: First-Line Nucleoside Analogs
MOA: Inhibit HBV replication through incorporation into viral DNA by
the HBV ___
- Results in DNA ___
___ (TDF, Viread®)
- Potential ALT flares on withdrawal
___ (TAF, Vemlidy®)
- renal impairment
___ (Baraclude®)
- Take on empty stomach
other NA:
- Lamivudine: 65-69% resistance at 5 years
- Adefovir: 20-29% resistance at 5 years
- Telbivudine: 11-25% resistance at 2 years
- reverse transcriptase
- chain-termination
- Tenofovir
- Tenofovir alafenamide
- Entecavir
HBV: First-Line Cytokine
MOA: Cytokine with antiviral, antiproliferative, and immunomodulatory effects
___ alfa 2a
- Contraindicated in patients with current psychosis, severe depression, neutropenia, thrombocytopenia, symptomatic heart disease, ___ disease, and uncontrolled seizures
Interferon alfa daily or three times weekly
- Peginterferon
- liver
HBV reactivation
Patients who test positive for both anti-HBc and ___ have a higher
reactivation risk compared to patients who test positive for both
anti-HBc and anti-HBs
HBsAg
Special Populations
Renal insufficiency – adjust dose of ___
Pregnancy
- treat pregnant women with HBV DNA > 200,000 IU/mL with ___
HIV coinfection
- Fully suppressive three-drug therapy should be initiated against HIV when treatment for HBV is warranted to decrease risk of resistance
- Combination emtricitabine/tenofovir (Truvada®, Descovy®) is
frequently used
- nucleoside analog
- tenofovir DF
HCV: Diagnosis & Serologic Testing
- anti-HCV is detectable 8-11 weeks after infection (indicates past exposure)
- ___ is diagnostic of current HCV infection
CDC recommends universal HCV screening for all US adults
and all pregnant women during every pregnancy
- HCV RNA
HCV
T or F: All DAAs carry a warning of risk of Hepatitis B Virus reactivation
TRUE
- Hepatitis B serologies should be checked prior to DAA initiation
HCV Therapeutic Agents
Direct Acting Antivirals (DAAs)
* ___ protease inhibitors
* ___ polymerase inhibitors (Nucleoside/Nucleotide, Nonnucleoside)
* ___ replication complex inhibitors
Ribavirin
Interferons
- NS3/4A
- NS5B
- NS5A
NS3/4A Protease Inhibitors
- NS3/4A serine protease cleaves the HCV RNA- encoded ___ into its functional units
- potent ___ inhibitors
- Agents in this class have a low barrier to resistance
(-previr): Boceprevir, Telaprevir, Simeprevir, Peritaprevir , ___ , ___ , ___
other 2 withdrawn
- polyprotein
- CYP3A4
- Grazoprevir, Glecaprevir, Voxilaprevir
NS3/4A Protease Inhibitors
Peritaprevir 150mg po daily with food
- Required ___ -boosting for once daily administration
Grazoprevir 100mg po daily with or without food
- Patients should have ALT checked at 8 weeks; discontinue if >5xULN
Glecaprevir 300mg po daily with food
- ___ tabs PO daily
Voxilaprevir 100mg po daily with food
- approved for patients who have been previously treated with an ___ replication complex inhibitors
- ritonavir
- 3
- NS5A
NS5B Polymerase Inhibitors
Inhibit the RNA NS5B polymerase responsible for
___ of HCV
MOA
1) Nucleotide analog ___ for the enzyme active site (high barrier)
2) Nonnucleoside agent binds to an ___ site inhibiting polymerase activity (low barrier)
(-buvir)
- replication
- competes
- allosteric
NS5B Polymerase Inhibitors
___ (nucleotide analog) (Sovaldi®) 400mg po daily with or without food
___ (nonnucleoside analog) 250mg po BID
- withdrawn
- Sofosbuvir
- Dasabuvir
NS5A Replication Complex Inhibitors (-asvir)
Inhibit the protein NS5A, needed for HCV RNA
replication and ___
- Low barrier to resistance, but are very potent
___ 90mg po daily with or without food
- No dosage adjustment needed in hepatic impairment
Ombitasvir 25mg po daily with food
- withdrawn
Daclatasvir (Daklinza®) 60mg po daily with or without food
- withdrawn
___ 100mg po daily with or without food
- Prior to use in patients with genotype 1a, an NS5a genotype must be performed to screen for presence of resistance-associated substitutions (RASs) at baseline
___ 100mg po daily with or without food
- Prior to use in compensated cirrhotic patients with genotype 3, an NS5A genotype must be performed to
screen for presence of the Y93H substitution (9% prevalence); presence requires added ___ or
voxilaprevir
___ 120mg po daily with food
- Only available in coformulated Mavyret®
assembly
Ledipasvir
Elbasvir
Velpatasvir
- ribavirin
Pibrentasvir
Ribavirin
Weight-based dose
- 1000mg if < 75kg or 1200mg if > 75kg, in 2 divided doses with food
___ – category X
Contraindicated in patients with creatinine clearance < ___ mL/min
Monitor CBC
* Decrease dose if Hgb <10 g/dL
* Discontinue if Hgb <8.5 g/dL
* May use epoetin or darbepoetin to stimulate red blood cell production
- Teratogenic
- 50
