Therapeutics III Exam 4

• what are major RFs for acquiring HBV?

  -Infants born to infected mothers

  -International travelers to endemic areas

  -MSM

  -Multiple heterosexual partners

  -Injection drug users

  -Contaminated blood, organ transplants, blood products

  -Health care providers who work with blood

  -Developmentally disabled persons

  -Patients on dialysis

  -Persons with HCV or HIV

  -Persons with DM
• what are some LOW-risk risk factors for acquiring HBV?


  -Recipients of blood products

  -Health care workers in contact with blood

  -Chronic hemodialysis

  -Multiple sex partners, MSM

  -HIV infection

  -Unregulated body piercings & tattoos

  -Household contact with person who has Hep C (toothbrush, razor)
• Where are the areas of highest prevalence of Hepatitis B Virus?

  Africa, South America, East Asia, and Pacific Islands
• HBeAg


  hepatitis B envelope antigen
• what does IgM signify?

  active infection
• HCV is a ____-stranded ______ virus

  single; RNA
• How often does acute HCV infection resolve on its own (i.e., does not progress to a chronic infection)?

  acute hepatitis C persists for less than 6 months
• when is antiviral therapy indicated for HBeAg positive (common)?

  Treat when persistently elevated ALT (2x ULN) or elevated HBV DNA levels >20,000 IU/mL
• "The ideal treatment should induce a biochemical response (_________________), histological response (decrease liver inflammation documented on biopsy scores), and serologic conversion ___________________________________"

  (normalize ALT levels);

  (detectable antiHBe, antiHBs, and HBsAg loss)
• what are the three "first line" antivirals for CHB?

  -Entecavir

  -Tenofovir

  -Pegylated (peg) IFN-a2a
• Which agents are no longer recommended empirically due to resistance?

  Adefovir and lamivudine
• How does the patient's HIV status affect agent choices CHB?

  -With all oral HBV agents, HIV resistance may develop if given as monotherapy; therefore, test for HIV prior to starting a single anti-HBV agent-Patients coinfected with HIV and HBVshould receive concomitant highly active antiretroviral therapy (HAART) with an HBV agent
• ADEs for entecavir

  headache, dizziness, upset stomach, ALTs

  
  

  should be given on an empty stomach (at least 2 hrs before or after a meal)
• ADEs for tenofovir

  -generally, well tolerated

  -rare but significant adverse effects include nephrotoxicity and Fanconi syndrome, decreased bone mineral density, and osteomalacia

  
  

  take on empty stomach
• ADEs of adefovir

  asthenia, abdominal pain, diarrhea, dyspepsia, headaches, nausea, and flatulence, nephrotoxicity

  
  

  take with or without food
• ADEs of lamivudine

  -minimal and include fatigue, diarrhea, nausea, vomiting, and headaches

  -monitor ALT levels

  
  

  taken with or without food
• What are the advantages of interferon therapy in CHB?

  PegIFN-α2a (Pegasys) is the only IFN therapy approved for HBV that is effective in suppressing, and in some casesceasing viral replication without inducing resistance
• What are the disadvantages of interferon therapy?


  need for subcutaneous injections and a pronounced adverse-effect profile that may require dosage reductions or treatment discontinuation
• tenofovir inhibits _______ and HBV replication

  HIV
• Tenofovir disoproxil fumarate (TDF) has been used historically, but tenofovir alafenamide (TAF) was recently added to the CHB guidelines. What is the benefit of using tenofovir alafenamide in terms of toxicity?

  TAF delivers the prodrug tenofovir directly to hepatic cells intracellularly -->

  this results in lower concentrations in the kidneys and bones
• What is an "SVR" related to hepatitis C treatment?

  The primary goal of HCV treatment is to achieve a sustained virologic response (SVR), defined asundetectable HCV RNA levels at 12 weeks or longer after treatment completion
• What noteworthy adverse effects does ribavirin cause? How can you address this?

  -dermatological rash (recommend creams, lotions, oral antihistamines)

  -hemolytic anemia (monitor HgB, chest pain, reduce dose if HgB <10g/dL or significant symptoms)
• What concomitant infection should be addressed before initiating HCV therapy?

  Prior to administering any DAA regimen, the presence of HBV should be excluded because cases of HBV reactivation have occurred, leading to fulminant hepatitis or death. Patients positive for HBV should be treated either prior to or concomitantly with the DAA.

  Patients not immune against HBV should receive the HBV vaccine.
• Patients with decompensated cirrhosis (Child-Pugh Class B & C) should avoid which class/agents?

  Patients with decompensated Child-Pugh B and Child-Pugh C cirrhosis should not receive DAA regimens that include aprotease inhibitor (eg, voxilaprevir, grazoprevir, and glecaprevir)because hepatic decompensation and/or failure, need for transplant, or death may occur
• What cardiac medication interacts with nearly all DAAs? What reaction could occur?

  amiodarone --> inc risk of bradycardia
• Which drug interaction checker is recommended in the text?

  Clinicians may use the University of Liverpool’s Hepatitis Drug Interactions website,https://www.hep-druginteractions.org/checker, to assess for DDI
• Sofosbuvir available outside of a co-formulated tablet. Can it be used asmonotherapyin HCV?

  NO, no single agents -at least two DAAs (+/- ribavirin)
• Ledipasvir


  -NS5A inhibitor

  -OK to use in decompensated cirrhosis

  -DIs: BCRP, acid suppressing agents, severe renal impairment/ESRD
• Elbasavir

  -NS5A inhibitor

  -OK to use in decompensated cirrhosis

  -DIs: OATP1B1/3, CYP3A
• Grazoprevir

  -NS3/4A inhibitor

  -CANNOT use in decompensated cirrhosis

  -DIs: ATP1B1/3, CYP3A
• Voxilaprevir

  -NS3/4A protease inhibitor

  -CANNOT use in decompensated cirrhosis

  -DIs:

  P-gp

  BCRP

  OATP1B1/3

  OATP2B1

  CYP2B6

  CYP2C8

  CYP3A4

  Acid suppressing agents

  Severe renal impairment
• What is unique about Sofosbuvir/Velpatasvir/Voxilaprevir (Vosevi)'s indication/role in therapy compared to other

  DAAs?

  contains drugs targeting three different sites to inhibit HCV viral replication
• What labs should be drawn to monitor for safety if a patient is on interferon therapy?

  LFTs, hemoglobin, CBC with differential, ANC, derm
• According to the guidelines, who is NOT eligible for the "simplified treatment" algorithm?

  -Prior Hep C treatment

  -Cirrhosis

  -HBsAg positive

  -Current pregnancy

  -Known or suspected hepatocellular carcinoma

  -Prior liver transplantation
• What two agents are recommended under the "simplified treatment"?

  Glecaprevir and Sofosbuvir
• ZEPATIER (Elbasvir /Grazoprevir)

  Genotype 1a and 1b duration

  12 weeks (for both noncirrhotic and compensated)
• ZEPATIER (Elbasvir /

  Grazoprevir) genotype 2

  not a recommended regimen
• MAVYRET Glecaprevir /

  Pibrentasvir) genotype 1a, 1b, and 2 duration

  8 weeks (for both noncirrhotic and compensated)
• HARVONI (Ledipasvir /Sofosbuvir) duration for gentotype 1a, 1b

  Noncirrhotic: 12 weeks

  Compensated: 12 weeks

  Decompensated: 24 weeks

  Decompensated + RBV: 12 weeks
• EPCLUSA (Velpatasvir /Sofosbuvir)

  genotype 1a, 1b, 2Noncirrhotic: 12 weeks

  Compensated: 12 weeks

  Decompensated: 24 weeks

  Decompensated + RBV: 12 weeks