Chapter 19: Hepatitis and Liver Disease Flashcards
Hepatitis A
- Acute
- Fecal-Oral transmission
- Yes vaccine
- 1st line tx is supportive care
Hepatitis B
- Acute and Chronic
- Blood and body fluid transmission
- Yes vaccine
- 1st line tx PEG-INF or NRTI (tenofovir or entacavir)
Hepatitis C
-Acute and Chronic
-Blood and body fluid transmission
-No vaccine
-1st line tx for tx naïve: DAA combination
Other tx: DAA combo + RBV or
DAA combo + RBV + PEG-INF
DAA mechanisms: NS3/4A Protease Inhibitors
-previr
P for PI
Glecaprevir
Grazoprevir
Paritaprevir
Voxilaprevir
*PIG
protease inhibitors and grub (take with food)
DAA Mechanisms: NS5A Replication Complex Inhibitors
-asvir
A for NS5A
Elbasvir Ledipasvir Ombitasvir Pibrentasvir Velpatasvir
DAA Mechanism: NS5B Polymerase Inhibitors
-buvir
B for NS5B
Dasabuvir
Sofosbuvir
All DAAs boxed warning, warnings, side-effects
Boxed: Risk of reactivation of HBV; test all patients prior to starting DAA
Warning: for sofosbuvir containing regimes do not use amiodarone serious symptomatic bradycardia
SE: well-tolerated
Epclusa
sofosbuvir/velpatasvir
sofosbuvir monotherapy not recommended
administer in original container
avoid or minimize acid-suppressive therapy
Mavyret
Glecaprevir/pibrentasvir
Take with food
Tx for pan-genotypic (all 6 genotypes) for tx naïve pts
- Epclusa
- Mavyret
Tx for salvage therapy
- Mavyret
- Vosevi (sofosbuvir/velpatasvir/voxilaprevir)
Tx for 8 week therapy (select patients)
-Mavyret
Tx for HCV/HIV co-infection
- Epclusa
- Harvoni (sofosbuvir/ledipasvir)
- Mavyret
Tx for children with certain genotypes
- Solvadi (sofosbuvir) and Harvoni (age >=3 years)
- Epclusa (age >=6 years)
- Mavyret (age >=12 years)
Viekira Pak Dose and CI
Paritaprevir/ritonavir/ombitasvir qam
and
Dasabuvir bid with meals
CI: use with cyp3A4 substrates or inducers and use with ethinyl estradiol products
Viekir Pak Warnings
Hepatic decompensation/failure in patients with cirrhosis, increased LFTs, significant drug interaction potential
Zepatier CI, Warnings
Elbasvir/grazoprevir
CI: Strong inducers of cyp3A4
Warnings: increased LFTs, significant drug interaction potential
All DAA CI
Strong inducers of CYP3A4: carbamazepine, oxcarbezapine, phenobarbitol, phenytoin, rifampin, rifabutin, and St. John’s Wort
Harvoni, Epclusa, and Vosevi DI
Antacids, H2RAs, and PPIs can decrease concentrations of ledipasvir and velpatasvir
PPIs are not recommended with Epclusa
Viekira Pak DI
Strong inducers of CYP3A4 (carbamazepine, oxcarbezapine, phenobarbitol, phenytoin, rifampin, rifabutin, and St. John’s Wort)
ethinyl estradiol containing products, lovastatin, simvastatin
Ribavirin MOA
Oral antiviral that inhibits replications of RNA and DNA viruses
Never used as monotherapy
Ribavirin CI, Boxed Warnings
CI: Pregnancy
Boxed Warning: significant teratogenic effects, not effective as monotherapy for HCV, hemolytic anemia
Ribavirin SE, Notes
SE: Hemolytic anemia
Notes: avoid pregnancy in female patients (including in female partners of male patients) during therapy, and 6 months after completion; use at least 2 reliable forms of contraception during and for 6 months after
Interferon Alfa MOA
Interferons are naturally produced cytokines that have antiviral, antiproliferative, and immunodmodulatory effects.
Approved for tx of HBV and HCV
PEG-ING-alfa has polyethylene glycol which prolongs half-life
INF-alfa Boxed warnings
Can cause or worsen neuropsychiatric, autoimmune, ischemic or infectious disorders
If used with ribavirin, teratogenic/anemia risk
INF-alfa Side Effects
-CNS effects (fatigue, depression)
-GI upset
-Increased LFTs (5-10x the ULN during tx)
-myelosuppression
Flu like syndrome (fever, chills, headache, malaise) pre-treat with apap and antihistamine
Nucleoside/Tide Reverse Transcriptase Inhibitors
NRTIs
Inhibit HBV replication by inhibiting HBV polymerase resulting in DNA chain termination
All HBV NRTIs Dosing, Boxed Warnings
Dosing: CrCl <50 decrease dose or frequency
Boxed Warnings: Lactic acidosis and severe hepatomegaly with steatosis which can be fatal. Exacerbations of HBV
Viread
Tenofovir disoproxil fumarate (TDF)
Preferred therapy
SE: renal impairment, decrease bone density
Warnings Fanconi syndrome
(NOF; nephrotoxicity, osteoporosis, Fanconi syndrome)
Vemlidy
Tenofovir alafenamide (TAF)
Preferred therapy
SE: nausea
Entecavir
Baraclude
Preferred therapy
Take on an empty stomach
Epivir HBV
Lamivudine
Do not use Epivir HBV for tx of HIV
SE: headache, n/v/d
Lab Test for Liver Disease: Acute Liver Toxicity
Increased AST/ALT
Lab Test for Liver Disease: Chronic Liver Disease
Increased AST/ALT, Alk Phos, Tbili, LDH, PT/INR
Decreased Albumin
Lab Test for Liver Disease: Alcoholic Liver Disease
Increased AST > increased ALT (AST will be about double ALT), increased GGT
Lab Test for Liver Disease: encephalopathy
Increased ammonia
Lab Test for Liver Disease: Jaundice
Increased Tbili
Child-Pugh Score
Class A (mild disease) >7 Class B (moderate disease) 7-9 Class C (severe disease) 10-15
MELD Score
The higher the numbers indicate a greater risk of death within 3 months
Drugs With a Boxed Warning for Liver Damage
- Apap (high doses, acute or chronic)
- Amiodarone
- Isoniazid
- Ketoconazole (oral)
- Methotrexate
- Nefazodone
- NNRTIs
- NRTIs
- Propylthiouracil
- Tipranavir
- Valproic Acid
Octreotide
Sandostatin
Selective for splanich vessels to stop bleeding
SE: bradycardia, cholelithiasis, billiary sludge
Vasopressin
Vasostrict
Non-selective
Antidiuretic hormone analog
Non-selective Beta-Blockers for Portal Hypertension
Work by 2 mechanisms
- decrease cardiac output via beta-1 blockade
- decrease splanich blood flow due to vasoconstriction (via beta-2 blockade and alpha activity)
Beta-Blockers for Portal Hypertension
Nadolol (corgard)
Propranolol (inderal la, inderal XL
Beta-Blocker for Porta Hypertension Boxed warnings, warnings
Boxed warnings: do not withdraw beta-blocker abruptly
Warning: non-selective drugs are used to portal hypertension, use extreme caution in asthma, severe cop, PVD
Lactulose for Hepatic Encephalopathy MOA
Works by converting ammonia produced by intestinal bacteria to ammonium which is polar and therefore cannot readily diffuse into the blood
Lactulose SE
Flatulence, diarrhea, dyspepsia, abdominal discomfort
Rifaximin
Xifaxin
Neomycin
Neurotoxicity
GI upset
Ratio of furosemide to spironolactone
40mg furosemide to 100mg spironolactone to maintain potassium balance
