hepatitis meds

Question 1

Causes of Hepatitis

Answer 1

• viral hepatitis
• alcoholic hepatitis
• toxic&drug induced hepatitis
• autoimmune
• nonalcoholic fatty liver disease
• ischemic hepatitis
• giant cell hepatitis

Question 2

Which types of viral hepatitis are acute only?

Answer 2

A & E

Question 3

Which types of viral hepatitis are fecal-oral transmission?

Answer 3

A & E

Question 4

Hepatitis A Virus

Answer 4

• transmission: fecal-oral
  
  • close-personal contact
  • blood exposure (rare)
• Incubation:
  
  • approx 30 days; 4 weeks; 1 month
• Detection of acute infx:
  
  • HAV-IgM antibodies in serum
• Detection of immunity:
  
  • serum HAV-IgG
• Detecting HAV RNA:
  
  • RT-PCR: reverse transcriptase PCR
• No tx → supportive care (nearly all recover within 6 months)

Question 5

HAV Prevention

Answer 5

promote proper sanitary practice

frequent hand washing

safe food prep

Question 6

HAV Prevention - Immune Globulin

Answer 6

• Passive immunization:
  
  • IM polyclonal serum immune globulin
    
    • we administer antibody into the person
  • body does not amount an immune response, it just gets immunity
• Pre-exposure:
  
  • at least 14 days before exposure
  • travelers to intermediate and high HAV-endemic regions
    
    • <3 months: 0.02mL/Kg
    • ≥ 3 months: 0.06mL/Kg (q4-6mo)
• Post-Exposure:
  
  • within 14 days of exposure
  • household or other intimate contacts
    
    • 0.02mL/kg
  • institutions
  • common source exposure (i.e. food made by infected person)

Question 7

Who should be vaccinated against HAV?

Answer 7

children > 1 yr

persons who are at risk for infx or complications

• Adults should receive 2 dose series at least 2 weeks prior to expected HAV exposure
• different vaccine, not immunoglobulin
  
  • these are antigen-initiated immune responses
• VAQTA & HAVARIX = hep A only
  
  • VAQTA: <18: 25 units, ≥ 19: 50 units
  • HAVARIX: ≤ 18: 720 units, ≥ 19: 1550 units
• TWINRIX = Hep A & B
  
  • only ≥ 18: 720U/20mcg (HBsAg)
    
    • 3 dose: 0, 1, 6
    • 4 dose: 0, 7d, 21-30d, 12 months

Question 8

Hepatitis B Virus

Answer 8

dsDNA

surface antigen, core antigen, E antigen

• Transmission: vertical transmission is most common in high prevalence areas
  
  • close contact (children) in intermediate prevalence areas
  • unprotected Sex & IV drug use in adults in low prevalence areas
• incubation: ~60-90 days, 2-3 months
• Acute infx:
  
  • HBsAg
• Viral replication:
  
  • HBeAg
    
    • demonstrates active & rapid viral replication
• Active infx, viral replication:
  
  • HBV DNA
    
    • guides management of chronic infx
• Immunity to infx:
  
  • Anti-HBs
• inactive infx:
  
  • Anti-HBe
• Resolution of infx:
  
  • Anti-HBc
    
    • immunized pts do not produce Anti-HBc

Question 9

HBV immune tolerant phase

Answer 9

HBeAG (+)

Viral load > 20K IU/mL

ALT/AST relatively normal

Question 10

HBV Immune Active Phase

Answer 10

HBeAg (+)

→ virus is replicating

elevated viral load & ALT/AST

Question 11

HBV Inactive chronic hepatitis B Phase

Answer 11

• Viral load = low or undetectable <2K
• ALT/AST normal
• HBeAG (-)
  
  • virus not replicating
• Anti-HBe present

Question 12

HBV Immune Reactivation Phase

Answer 12

• HBeAg (-)
  
  • virus not replicating
• increased VL & AST/ALT
• among those who seroconvert from HBeAG (+) to Anti-HBe → 10-30% will continue to have high ALT/AST & viral loads

Question 13

Normal ALT levels for men & women

Answer 13

• men: < 30U/L
• women: <19 U/L

Question 14

When to tx: HBeAg Positive: ALT≤ ULN, ALT > ULN but <2x ULN, ALT ≥ ULN

Answer 14

Question 15

When to Tx: HBeAg negative, ALT ≤ ULN, ALT > ULN but < 2x ULN, ALT ≥ 2x ULN

Answer 15

Question 16

Tenofovir, TDF

Answer 16

used for HBV

prodrug

• Preferred in pregnancy
• do not D/C abruptly
• caution in HIV/HBV co-infected patients
  
  • ritonavir (HIV antiretroviral therapy) will boost levels of tenofovir
• Renal dose adjustments when CrCl ≤ 50mL/min
• does not last as long as tenofovir alafenamide
• SEs:
  
  • Fanconi syndrome:
    
    • kidney tubule disorder, excrete glucose, bicarb, phosphate, K+, amino acids
      
      • should add a CMP + phosphorus
  • Osteomalacia and decreased bone density

Question 17

Tenofovir alafenamide, TAF

Answer 17

• prodrug of tenofovir
• Not for CrCl < 15mL/min
• more stable in plasma → less renal/bone toxicity
• SEs:
  
  • lactic acidosis
    *

Question 18

Entecavir

Answer 18

adults & peds ≥ 2 yo for HBV

do not D/C med abruptly, can cause Hep B flare

• Renal dose adjustments when CrCl ≤ 50mL/min
• highest potency
• SEs:
  
  • lactic acidosis and hepatic steatosis
  • rash, N/V/D , HA, fatigue, abd pain,
  • increased LFTs, increased bilirubin

Question 19

Peginterferon alfa-2a

Answer 19

• can be used for all genotypes (A-J) of HBV
• MOA: antiviral, antiproliferative, immunomodulator
• indications:
  
  • adults with HBeAg (+) or (-)
  • compensated liver disease
  • evidence of viral replication and liver inflammation
• • Renal dose adjustments when CrCl ≤ 30mL/min
• can increase dose of methadone (opioid) and theophylline
• Contraindications:
  
  • ANC < 500, platelet < 90K
  • infants and neonates
  • autoimmune hepatitis, decompensated liver
• adverse effects:
  
  • suicidal ideation!!
  • flu-like sxs (1-2 hours post admin = Most common
  • worsen anxiety
  • rash, hair loss, dry skin

Question 20

How do we identify if HBV is replicating?

Answer 20

if HBeAg is positive

Question 21

HBV prevention: screening & passive IZ

Answer 21

• screening for high risk populations
• Passive immunization (pt is given antibody):
  
  • polyclonal serum immune globulin (HBIG)
  • Post-exposure (most effective within 48 hours)
    
    • may also be given to neonates who are at increased risk of contracting hep B (HBsAg and HBeAg positive)

Question 22

HBV vaccination

Answer 22

• adults and adolescents:
  
  • three dose series (0, 1, 6 mo)
• post-exposure prophylaxis:
  
  • first dose given asap (within 12 hours of exposure)
    
    • next two doses follow usual schedule
• infants:
  
  • birth, 1-2 months of age, 3rd dose: no earlier than 6 mo

Question 23

HCV

Answer 23

+ ssRNA

• acute and chronic
  
  • 75-85% will develop chronic HCV
• 1a, 1b and 2-6 genotypes
• bloodborne
• takes 4 weeks after infx before development of antibodies

Question 24

Who to screen for HCV?

Answer 24

• once for everyone ≥ 18yo
• everyone < 18 with risky behaviors, exposures etc
• annual HCV testing for IV drug users and for HIV infected men who have unprotected sex with men
• Risk behaviors:
  
  • IV drug use
  • intranasal illicit drug use
  • men who have sex with men
• Risk exposures:
  
  • hemodialysis, healthcare after needlestick
    *

Question 25

HCV genotype 1a tx

Answer 25

Question 26

How to screen for HCV

Answer 26

* HCV antibody: * **not useful in acute phase**, takes at least 4 weeks after infx before development of antibodies * HCV RNA * qualitative and quantitative * alose used to monitor the response to antiviral therapy * Should screen for HCV genotype: 1a, 1b, 2-6

Question 27

NS3-4A protease inhibitors

Answer 27

used for HCV * **simeprevir** * **paritaprevir** * **grazoprevir** * **asunaprevir**

Question 28

NS5A drugs

Answer 28

used for HCV “asvir” * **ledipasvir** * **ombitasvir** * **daclatasvir** * **elbasvir**

Question 29

Sofosbuvir/ Velpatasvir (Epclusa)

Answer 29

used to tx HCV * _indications_: * All HCV genotypes (1-6) * without cirrhosis * compensated cirrhosis * decompensated cirrhosis: epclusa + ribavirin * _SEs_: * HA, N/D, fatigue, insomnia (coming from sofosbuvir→ fati, insom)

Question 30

Glecaprevir/Pibrentasvir (Mavyret)

Answer 30

used to tx HCV→ **top of the list to tx HCV** * _MOA_: * **glecaprevir**: protease inhibitor * **pibrentasvir**: NS5A inhibitor * _contraindications_: * child-pugh B or C * together with atazanavir or rifampin * _SEs_: * HA, fatigue, nausea, diarrhea

Question 31

HCV genotype 1b, 2-6 tx

Answer 31

Question 32

NS5B Polymerase Inhibitor Drugs

Answer 32

used to tx HCV “buvir” * Dasabuvir * Beclabuvir

Question 33

Most common genotype of HCV

Answer 33

1

Question 34

Ledipasvir-Sofosbuvir (Harvoni)

Answer 34

very popular drug used to tx HCV→ **top of the list for tx of HCV** * Ledipasvir: NS5A * Sofosbuvir: NS5B * swallow tablet whole, do not crush or chew * _SE_: * fatigue, HA, insomnia, N/V

Question 35

Ribavirin

Answer 35

used to tx HCV for all genotypes 1-6 and HCV/HIV co-infection ≥ 5 years old * _contraindications_: * pregnancy * **autoimmune hepatitis, hemoglobinopathies** * _Adverse effects_: * **hemolytic anemia** * worsen cardiac disease, fatigue, headache, nausea, anorexia, insomnia, myalgia

Question 36

Child-Pugh Score (CPS)

Answer 36

* measures how severe the chronic liver disease is → including cirrhosis * used to determine drug dosing in hepatic impairment

Question 37

Is HCV immune globulin recommended for pre-exposure or post exposure prophylaxis?

Answer 37

No

Question 38

Bugs associated with spontaneous bacterial peritonitis

Answer 38

* E.coli, Klebsiella, Strep pneumoniae

Question 39

Tx of Spontaneous Bacterial Peritonitis

Answer 39

* _Empiric_: Cefotaxime \> ceftriaxone * ofloxacin * _Prophylaxis_: * ceftriaxone * norfloxacin * Bactrim

Question 40

Variceal Bleed Prophylaxis

Answer 40

Beta blockers: non-specific * propranolol * nadolol

Question 41

Tx of Hepatic Encephalopathy

Answer 41

* **Lactulose (constulose, enulose, generlac**) * MOA: limit GI bacteria that cause ammonia * lactulose metabolized to lactic acid in GI → convert NH3 to NH4+ * \*\*\**Titrate to 2-3 soft bowel movements\*\*\** * SEs: * flatulence, diarrhea, abd pain, dehydration, hypernatremia, hypokalemia * **Rifaximin**: * not absorbed systemically * _Ses_: * flatulence, dizziness, nausea, ascites

Question 42

When to tx HBV

Answer 42

Question 43

Elbasvir & Grazoprevir (Zepatier)

Answer 43

* used for HCV genotype 1 & 4 * adverse effects: * fatigue, headache, nausea * DO NOT USE IF RAS (resistance associated substitution)

Question 44

How long is the tx for HCV?

Answer 44

8-12 weeks