Hepatitis/Liver Disease Flashcards
Hep A is chronic or acute?
acute
Transmission of HAV
fecal-oral
- improper handwashing
- contaminated food/water
HAV symptoms are usually ____ and ____
mild and non-specific
HBV and HCV are usually acute or chronic
BOTH!
acute illness that can lead to chronic infection, cirrhosis, cancer, liver failure, and death
HBV/HCV transmission
infectious blood or body fluids
Which hepatitis does NOT have a vaccine?
HCV
HAV first line tx
supportive
HBV first line tx
PEG-INF or NRTI (tenofovir or entecavir)
HCV first line treatment naive
DAA (direct acting antivirals) combination
How many HCV genotypes are there?
6
What three things determine HCV therapy?
- genotype
- presence of cirrhosis
- treatment naive?
What is a prefered HCV regimen?
2-3 DAAs with different mechanisms
What is the prefered duration of HCV treatment?
8-12 weeks
Ritonavir role in HCV treatment
dose not have action against HCV itself, but used to boost levels of HV protease inhibitors
Interferon’s role in HCV
no recommended in combination therapy can be considered if DAAs are CI or too expensive
Treatment options for treatment-naive patients without cirrhosis
glecaprevir/pibrentasvir
sofosbuvir/velpatasvir
Three types of DAA mechanisms
- NS3/4A Protease inhibitor
- NS5A Replication Complex Inhibitor
- NS5B Polymerase Inhibitor
list of Ns3/4A PIs
"-previr" P for PI glecaprevir grazoprevir paritaprevir voxilaprevir
list of NS5A replication complex inhibitors
"-asvir" A for NS5A ledipasvir ombitasvir pibrentasvir velpatasvir
list of NS5B Polymerase inhibitors
“-buvir” B for NS5B
dasabuvir
sofosbuvir
Protease Inhibitors should be taken with or without food?
with food! PIG (PIs and Grub)
What do patients need to be tested for before starting a DAA
HBV - risk of reactivating
Sofosbuvir specific warnings
- do not take with amiodarone -> serious symptomatic bradycardia possilbe
- risk of hypoglycemia when used with insulin
Side effects of DAAs
typically well tolerated
- HA, fatigue, diarrhea, nausea
What to monitor with DAAS
LFTs (bilirubin)
HCV-RNA
Sovaldi
Sofosbuvir
400mg daily
*dispense in original packaging
Epclusa
Sofosbuvir/velpatasvir
1 tablet daily
*dispense in original packaging
avoid acid-suppressive therapy
Harvoni
sofosbuvir/ledipasvir
1 tablet daily
*dispense in original packaging
avoid acid-suppressive therapy
Vosevi
sofosbuvir/velpatasvir/voxilaprevir
*dispense in original packaging
avoid acid-suppressive therapy
Mavyret
glecaprevir/pibrentasvir
3 tablets daily
*Take with food (glecaprevir)
CI: mod-severe hepatic impairment or decompensation
Technivie
paritaprevir/ritonavir/ombitasvir
*take with food (paritaprevir)
Viekira Pak
paritaprevir/ritonavir/ombitasvir+ dasabuvir
Tri - 2 tablets in the morning
dasabubvir - twice daily with meals
Zepatier
elbasvir/grazoprevir
Contraindication for Mavyret
mod-severe hepatic impairment or history of hepatic decompensation
Sofosbuvir monotherapy role
not effective/not recommended
Which drugs should be dispensed in original packaging?
Sovaldi, Epclusa, Harvoni, Vosevi
which drugs are approved for all 6 HCV genotypes (pan-genotypic)
Epclusa and Mavyret
Which drugs are approved for salvage therapy?
Vosevi and Mavyret
which drugs are approved for 8-week course of therapy?
Mavyret
which are approved for HCV/HIV co-infection
Epclusa, Harvoni, and Mavyret
which are approved for children 12 or older with certain genotypes
Sovaldi and Harvoni
Major warning with DAAs
LOTS OF DRUG INTERACTIONS
CI with strong ______ inducers
CYP3A4
-carbamazepine, oxcarbazepine, phenobarb, phenytoin, rafampin, rifabutin, St. John’s Wort
DAAs can increase the concentration of ______ leading to increased ________ risk
statins = increased MYOPATHY risk
Which drugs should Mavyret specifically not be used with
efavirenz
HIV PIs
ethinyl estradiol products
cyclosporine products
Which DAAs should not be used with PPIs
Epclusa
Ribavirin (RBV) MOA
inhibits replication of RNA and DNA viruses
RBV place in therapy
HCV in combo, never monotherapy
aerosolized has been used in RSV
boxed warnings for RBV
- teratogenic effections
- not effective monotherapy
- hemolytic anima (can worsen cardiac disease)
CI with RBV
pregnancy
women of childbearing age without reliable contraceptive use
men with pregnant female partners
CrCl <50
didanosine concomitant use (hepatic failure)
what limits use of interferons
toxicities
lab abnormalities
List of NRTIs used in HBV
TDF (Viread) TAF (Vemlidy) Entecavir (baraclude) Adefovir Lamivudine (Epivir HBV)
Which NRTIs should not be used with a HIV co-infection
lamivudine (Epivir), TAF, and TDF
- lower dose for HBV could lead to resistance in HIV treatment)
Presentation of cirrhosis
jaundice, dark urine, pain in upper right quad of abdomen, loss of appetite
Which labs indicate acute liver toxicity due to drugs or otherwise
elevated AST ALT
which lab indicate chronic liver disease
increase ast/alt, alk phos, tbili, ldh, pt/inr
decreased albumin
which lab indicates alcoholic liver disease
elevated ast about double the alt
increased ggt
which lab indicateds hepatic encephalopathy
increased ammonia
normal range for ast/alt
10-40 u/L
increased alk phos and Tbili indicates cholestatic or hepatocellular liver disease?
cholestatic
alt and ast = hepatocellular
increased alk phos, tbili, ast, and alt indicates what type of liver disease?
mixed!
primary treatment for drug-induced liver injury
Stop the drug!
When do we d/c a hepatotoxic drug?
when lfts are >3x upper limit of normal
Major hepatotoxic drugs
- APAP
- amiodarone
- isoniazid
- ketoconazole
- methotrexate
- nefazodone
- nevirapine
- NRTIs
- propylthiouracil
- tipranavir
- valproic acid
steatosis meaning
fatty liver
reversible if offending agent stopped (alcohol)
Inpatient alcohol withdrawal treatment
bzds
Medications meant to prevent alcohol relapses
naltrexone
acamprosate
disulfiram
Why is thiamine used in alcoholics?
prevent/treat Wernicke-Korsakoff syndrome - encephalopathy
Recommended first line treatment for esophageal varices
band ligation
sclerotherapy
Octreotide
selective vasoconstrictor for splanchnic vessels
used in varices to stop/slow bleeding
Vasopressin
non-selective vasoconstrictor used in varices to stop/slow bleeding
Secondary prevention of variceal bleeding
Non-selective beta-blockers
titrate to maximum tolerated dose
side effects of octreotide
bradycardia, cholelithiasis, biliary sludge
Which beta blockers are non-selective
nadolol
propranolol
how to beta-blockers prevent variceal bleeding
reduce portal pressure by decreasing CO and decreasing splanchnic blood flow via vasoconstriction
What causes symptoms of hepatic encephalopathy
accumulation of ammonia
symptoms of hepatic encephalopathy
musty odor of breath, changes in thinking, confusion, forgetfulness, asterixis
drug therapy for hepatic encephalopathy
lactulose
antibiotics like rafaximin
how does lactulose work
first line therapy for encephalopathy and prevetion
converts ammonia produced by intestinal bacteria to ammonium which cannot diffuse into the blood due to not being polar.
How do antibiotics help hepatic encephalopathy
decrease ammonia production by inhibitions activity of urease producing bacteria
lactulose treatment dosing
30-45 mL every hour until bowel movement then 30-45 mL 3-4 times daily titrated to produce 2-3 soft bowel movements dialy