Hepatitis B and Hepatitis C (Dr. Lam)

1. What are their genetic differences?

1. HAV: non-enveloped SS RNA

2. HBV: enveloped DS DNA (partial)

3. HCV: enveloped SS RNA

4. HDV: enveloped SS RNA

5. HEV: non-enveloped SS RNA

1. Which viral hepatitis are transmitted via fecal-oral route vs. blood-to-blood route? 

1. Fecal route: HAV and HEV

2. Blood-blood:HBV, HCV, HDV→ “BCD TOFU is spicy & red af”

1. Which viral hepatitis have vaccines for prevention of contracting the illnesses? 

1. HAV and HBV

   1. HAV: Havrix or Vaqta

   2. HBV: Heplisav-B

   3. HAV and HBV: Twinrix

1. Which viral hepatitis could cause chronic illness if left untreated?

1. HBV, HCV, HDV → BCD TOFU AGAIN

1. Which of the viral hepatitis could cause cirrhosis, HCC, and potentially death if left untreated?

HBV

1. What is the HBV vaccine that is only approved for adults (≥ 18 yo) and given in a series of two doses? 

Heplisav-B.

1. Name the available HBV vaccines and the number of doses to complete their series. 

1. Heplisav-B: 2 doses → completed in 1 month

2. Engerix-B and Recombivax B: 3 doses → given at 0, 1, and 6 months

3. Twinrix (HAV/HBV) 3 doses → given at 0, 1, and 6 months

1. : HBV infection can be cured (t/f)

false

1. According to the current AASLD/IDSA guidelines, list the 3 preferred oral antiviral agents for chronic HBV (CHB) treatment. (Please provide their generic and brand names). Explain why they are preferred over the older agents.

Entecavir, TAF, TDF

1. Which HBV antiviral agents are preferred in older patients (≥ 60 years old)?

ETV and TAF

1. Which HBV antiviral agent has safety and efficacy data for use in pregnant patients?

TDF

1. Which HIV antiretroviral agents are also FDA-approved for HBV treatment? (Select all that apply)

1. Emtricitabine (Emtriva®)

2. Lamivudine (Epivir-HB®)

3. Tenofovir alafenamide (Vemlidy®)

4. Tenofovir disoproxil fumarate (Viread®)

3,4

1. Based on the current AASLD/IDSA guidelines, the preferred oral antiviral agents for treating CHB infection include: (Select all that apply)

1. Entecavir (Baraclude®)

2. Tenofovir disoproxil fumarate (Viread®)

3. Tenofovir alafenamide (Vemlidy®)

4. Lamivudine (Epivir-HB®) 

5. Pegylated interferon alfa-2a (Pegasys®) 

1,2,3

1. A 29-year-old woman is 10 weeks pregnant and is diagnosed with CHB infection from her OB/GYN. She has NKDA and her renal function is WNL. Which antiviral treatment would be most appropriate for this patient?

1. Entecavir (Baraclude®)

2. Tenofovir disoproxil fumarate (Viread®) → with HBV DNA > 200,000

3. Tenofovir alafenamide (Vemlidy®)

4. Lamivudine (Epivir-HB®)
   
   

2

1. What antiviral medication is administered to neonates at risk of contracting HBV infection from their HBV-positive mothers? (Hint: this drug is an immunoglobulin) 

Hepatitis B immune globulin (HBIG)

1. A 34-year-old cisgender man with HIV is seen for a follow-up visit to start ART. His baseline laboratory studies show a CD4 count of 488 cells/mm3, HIV RNA 68,400 copies/mL, and no evidence of antiretroviral drug resistance. He also has CHB infection, and laboratory studies show a positive hepatitis B surface antigen (HBsAg), positive hepatitis B e antigen (HBeAg), and HBV DNA level of 18,800,000 IU/mL. He has no other medical problems and is not taking any other medications. You plan to promptly start HIV antiretroviral therapy for this patient. Which ART regimen would you choose?

1. Biktarvy® (BIC/TAF/FTC) → TAF is preferred oral antiviral for CHB & HIV

2. Triumeq® (DTG/ABC/3TC) → 3TC not preferred 

3. Dovato® (DTG/3TC) 

4. Cabenuva® (CAB + RPV) —> either drug is active against HBV

1

1. DC is a 27-year-old MSM who wants to take PrEP for HIV prevention. His baseline laboratory and hepatitis panel results are as follows:

HIV 1/2 Ab/Ag – negative HIV RNA – negative 

HAV Ab – positive HAV Ag – negative 

HBsAb – negative HBsAg – positive

HCV Ab – negative  

BUN/SCr = 22/0.9 mg/dL (eGFR ~80 mL/min/1.73)

Bacterial STIs (syphilis, gonorrhea, and chlamydia) – negative 

Which PrEP medication would you recommend for him? 

Based on the lab results, what other tests would you want to include for this patient? 

Which PrEP medication would you recommend for him? 

• Descovy

• Truvada

Based on the lab results, what other tests would you want to include for this patient? 

• ALT & AST

1. A 68-year-old male patient is HBsAg+ with an HBV DNA viral load of 1 million IU/mL. He has NKDA. He has mild renal insufficiency, but his CBC and chemistries are WNL. Based on the AASLD/IDSA guidelines, which HBV agents are preferred for this patient? (Select all that apply)

1. Entecavir (Baraclude®)

2. Tenofovir disoproxil fumarate (Viread®)

3. Tenofovir alafenamide (Vemlidy®)

4. Pegylated interferon alfa-2a (Pegasys®)

1,3

1. Which direct-acting antivirals (DAAs) belong to the NS3/4A serine protease inhibitor class? (Select all that apply) → end in -previr

1. Daclatasvir 

2. Ledipasvir

3. Simeprevir

4. Grazoprevir

5. Voxilaprevir

6. Dasabuvir

3,4,5

• -previr

1. Describe the mechanism of action of NS3/4A serine protease inhibitors. (FYI)

1. NS3/4A protease cleaves polyproteins into mature proteins

2. MOA: Inhibit protein synthesis and prevent viral maturation
   

1. List 2 NS5A inhibitors. Describe the mechanism of action of NS5A.

1. Ledipasvir, velpatasvir

2. MOA: Inhibit the phosphorylation of 5S5A (dimer protein) that is involved in HCV replication, assembly, and secretion

(-asvir)

1. List the main NS5B inhibitor used in coformulated DAA regimens. Describe the mechanism of action of the NS5B agent.

1. Sofosbuvir 

2. NS5B: RNA-dependent RNA polymerase

3. MOA: Block viral replication and subsequent translation

(-buvir)

1. List the 3 DAAs that have pangenotypic activity against all six HCV strains. What are the individual agents found in these DAA combinations?

1. Epclusa (NS5B/NS5A) - sofosbuvir/velpatasvir (SOF/VEL)

2. Vosevi (NS5B/NS5A/PI) - sofosbuvir/velpatasvir/ voxilaprevir (SOF/VEL/VOX)

3. Mavyret (PI/NS5A) - glecaprevir/pibrentasvir (GLE/PIB) → take with food to increase absorption (think of M for meal)

1. What is the main difference in the spectrum of activity between Harvoni® and Epclusa®? (Hint: genotype coverage)

1. Harvoni (ledipasvir/sofosbuvir) - genotypes 1, 4, 5, 6

2. Epclusa - genotypes 1-6

3. Zepatier (elbasvir/grazoprevir) - genotypes 1, 4

1. Name 2 drugs that can interact with Harvoni® (SOF/LDV). 

1. Sofosbuvir: Amiodarone (C/I with sofosbuvir) → serious bradycardia

2. Ledipasvir: pH dependent, can interact w/ antacids, H2RAs, PPIs

3. Potent P-gp inducers: Rifampin, CBZ, PHT, modafinil 

   1. DDIs ARE NOT ON THIS EXAM 

1. Which DAA regimen is taken as 3 tablets daily and with food to increase its absorption (AUC) and efficacy?

Mavyret

1. What 2 main side effects should be provided to a patient when taking Mavyret or Epclusa treatment? 

Fatigue, HA

1. The medical resident wants to prescribe Eplusa® for a person with chronic HCV (CHC) infection. He forgot the individual components of this DAA regimen and asks you for the information. What are the components of Epclusa®?

1. Elbasvir/grazoprevir → Zepatier

2. Ledipasvir/sofosbuvir → Harvoni

3. Ledipasvir/sofosbuvir/voxilaprevir  → Vosevi

4. Sofosbuvir/velpatasvir

4

1. A 45-year-old male is diagnosed with HCV infection, genotype 3. He is treatment-naive with no cirrhosis. Based on the AASLD HCV treatment guidelines, which DAA regimens and duration would be most effective for him? (Select all that apply)

1. Mavyret® for 8 weeks

2. Harvoni® for 12 weeks

3. Eplusa® for 12 weeks 

4. Zepatier® for 12 weeks

1,3

1. According to the AASLD HCV treatment guidelines, which of the following regimen is recommended for treatment-naïve patients with HCV genotype 2 and severe CKD (eGFR = 15 mL/min/1.73)?

1. Mavyret® (glecaprevir/pibrentasvir) for 8 weeks → also Zepatier, but it only covers genotypes 1, 4

2. Epclusa® (velpatasvir/sofosbuvir) for 12 weeks → safe in decompensated cirrhosis

3. Harvoni® (ledipasvir/sofosbuvir) for 12 weeks  → safe in decompensated cirrhosis

4. Vosevi® (velpatasvir/sofosbuvir/voxilaprevir) for 12 weeks → covers genotypes 1-6, but no CKD

1

• no dose adjust

• avoid sofosbuvir in CKD & kidney disease

HCV cure is synonymous with sustained viral load response (SVR), which is defined as achieving undetected or negative response 12 weeks after treatment completion. (t/f)

true

1. (True/False): Ribavirin can be given to pregnant women as part of their HCV infection treatment.

False

1. Name the 2 NS5A inhibitors that can interact with PPIs? What are the recommendations when taking these agents with PPIs? Which coformulated DAA regimens contain these NS5A inhibitors?

(NOT ON EXAM 2)

1. Velpatasvir, ledipasvir → Harvoni (SOF/LDV), Epclusa (SOF/VEL)

2. LDV: PPIs can be taking simultaneously under fasting conditions

3. VEL: Not recommended; if necessary, take w/ food 4 hours before PPI

1. A 48-year-old man is diagnosed with CHC infection, genotype 2. He is treatment-naïve with no signs and symptoms of cirrhosis. His Fibrosure score = 0.28 (F1 stage) and other pertinent labs are unremarkable. Which DAA regimens and duration of treatment would be effective for this patient? (Select all that apply)

1. Mavyret® for 8 weeks → safe in HD

2. Harvoni® for 12 weeks → genotypes 1, 4, 5, 6

3. Vosevi® for 12 weeks → covers genotypes 1-6, but pt is treatment naive (save for salvage therapy)

4. Epclusa® for 12 weeks

1,4

1. 
   A 58-year-old woman is diagnosed with CHC infection, genotype 4. She is treatment-naïve with some signs and symptoms of compensated cirrhosis. Her Fibrosure score = 0.68 (F4 stage) and other pertinent labs are unremarkable. Which DAA regimens and duration of treatment would be effective for this patient? (Select all that apply)

1. Mavyret® for 8 weeks  → genotypes 1-6, but not safe in cirrhosis

2. Harvoni® for 12 weeks → genotypes 1, 4, 5, 6

3. Vosevi® for 12 weeks → genotypes 1-6, but not safe in cirrhosis and not for treatment naive

4. Epclusa® for 12 weeks→ genotypes 1-6

2,4

• F3 & F4 (avoid PI)

1. Which of the following DAA regimens only contain NS5A and NS5B inhibitors? (Select all that apply)

1. Mavyret® (glecaprevir/pibrentasvir) 

2. Harvoni® (ledipasvir/sofosbuvir)

3. Eplcusa® (sofosbuvir/velpatasvir)

4. Zepatier® (elbasvir/grazoprevir)

5. Vosevi® (sofosbuvir/velpatasvir/voxilaprevir)

2,3

1. Which DAAs require an acidic environment for optimal absorption? (Select all that apply)

1. Velpatasvir → only NS5As (A for acidic)

2. Ledipasvir

3. Sofosbuvir

4. Grazoprevir

***NOT ON EXAM 2*

1,2

1. Which DAA regimens have pangenotypic activity (1-6 genotypes)? (Select all that apply)

1. Harvoni®

2. Vosevi®

3. Epclusa®

4. Mavyret®

5. Zepatier®

2,3,4

1. Which of the following pangenotypic DAAs could be given in HCV-infected patients on hemodialysis? 

1. Zepatier® → safe in HD, but not pangenotypic

2. Epclusa® → pangenotypic, but not given on HD (safe in decompensated cirrhosis like Harvoni)

3. Mavyret®

4. Vosevi® → pangenotypic, but not given on HD (not safe in decompensated cirrhosis)

3

1. A patient is diagnosed with HCV infection. Her Fibrosure score is 3 (moderate-to-severe cirrhosis). The physician wants to initiate her on Mavyret® (GLE/PIB). Do you agree or disagree with the treatment plan? 

1. DISAGREE: Mavyret is comprised of glecaprevir/pibrentasvir and PI regimens (glecaprevir) are contraindicated in moderate-severe liver impairment/cirrhosis can worsen liver function

2. Only treatment option would be Ecplusa, which is safe in cirrhosis and does not contain a PI 

Mavyret: okay to F0-F2

1. How should Epclusa® and Harvoni® be given with famotidine?

1. Administer simultaneously with (1 hour before or two hours after) or also 12 hours apart

1. A patient is on digoxin and amiodarone for CHF and atrial fibrillation management. She is diagnosed with HCV infection. Which DAA agent should not be included in her HCV treatment?

1. Ledipasvir

2. Dasabuvir

3. Glecaprevir

4. Sofosbuvir

4

Define chronic hepatitis B is what

HBsAg positive > 6 months

Drugs for Hepatitis B infection

Entecavir (baraclude)

TDF (Viread)

TAF (vemlidy)

patients with low level viremia and compensated cirrhosis should be treated, regardless of ALT (t/f)

true

all paints with decompensated cirrhosis who are HBsAG positive should be treated, regardless (t/f)

true

preferred first line monotherapoies for chronic hepatitis B —> in patients with renal dysfunction or bone disease

entecavir or tenofocvir AF (TAF)

for chronic hepatitis B therapy, when can it be stopped for cirrhosis

indefinite

for chronic hepatitis B therapy, when can it be stopped for HBeAg positive

consider discontinuation

for chronic hepatitis B therapy, when can it be stopped for HBeAg negative

indefinte

which drug is preferred for pregnant in Chronic Hepatitis B

TDF (Viread)

if HBV sAg is positive in hepatitis B what does it mean

patient has hepatitis B infection

Ab is positive in hepatitis what does it mean ?

patient is immunized

Anti-HCV & HCV RNA results mean what

acute or chronic HCV

Hepatitis C has no vaccine available but it is curable (t/f)

true

when a patient with CHC infection achieved SVR or cure from DAA treatment, they have developed immunity from being reinfected with HCV. (t/f)

false

name 2 drugs that can interact with harvoni (SOF/LDV)

Rifampin

Amiodarone

CBZ

PHT

modafinil

1. A patient is currently taking Mavyret® (GLE/PIB) for his CHC treatment. He is recently diagnosed with hyperlipidemia. His PCP wants to initiate him on a statin medication. Which HMG-CoA reductase inhibitor can this patient be started on without any dose adjustments? 

1. Rosuvastatin: max 10 mg, pravastatin: max 20 mg, pitavastatin: monitor dose