Liver Disease/Hepatitis Flashcards by Jimmy Hayden

Most common causes of viral hepatitis

hepatitis viruses A, B, C

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Hepatitis A info

Acute, self-limiting illness
transmitted via fecal-oral route (improper handwashing, contaminated water/food)
mild, non-specific symptoms

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Hep B and Hep C info

Can cause acute and chronic disease
Can lead to cirrhosis, liver cancer, liver failure and death
Transmission: via blood, bodily fluids of an infected individual
Requires antiviral therapy

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What vaccines are available for hepatitis?

Vaccines available for Hep A and Hep B

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Available agents used for Hep C treatment

NS3/4A protease inhibitor (-previr) p = PI
NS5A replication complex inhibitor (-asvir) A
NS5B polymerase inhibitor (-buvir) B

Combination of 2-3 meds is used for treatment

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How many genotypes of HCV are there? And what factors determine drug choice and duration of therapy in HCV>

6 genotypes
Factors:
Which genotype
treatment naiive?
\+/- cirrhosis

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Black boxed warning for HCV antiviral therapy

reactivating of HBV
Test all pt prior to starting meds

Not recommended to use sofosbuvir and amiodarone (severe bradycardia)

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Sofosbuvir monotherapy

Sovaldi
400 mg daily
Monotherapy not recommended
SE’s: HA, fatigue, diarrhea, nausea

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Sofosbuvir-containing combo therapies

Sofosbuvir + ledipasvir (Harvoni)
Sofosbuvir + velpatasir (Epclusa)
Sofosburvir + velpatasvir + voxilaprevir (Vosevi) [w/ food]

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Mavyret

glecaprevir + pibrentasvir
first med approved for 8 weeks duration (in pts w/o cirrhosis)
3 tabs daily WITH food

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Which meds are approved for all genotypes?

Epclusa (sofosbuvir + velpatasvir)

Mavyret (glecaprevir + pibrentasvir)

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Which meds are approved for HCV/HIV co-infection?

Epclusa (sofosbuvir + velpatasvir)
Mavyret (glecaprevir + pibrentasvir)
Harvoni (sofosbuvir + ledipasvir)

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What other drugs are available as a single drug tablet? [2]

Simeprevir (Olysio)
Take WITH food
NS3 Q80 K polymorphism testing might be recommended in some pts (consider different med if +)
Daclatasvir (Daklinza)
take in combo with sofosbuvir
3A4 metabolsim

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Technivie notes

Paritaprevir + ritonavir + ombitasvir
2 tabs QAM WITH FOOD
Warning in pts with cirrhosis (liver failure)
3A4 metabolism
women should avoid taking ethinyl estradiol

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Viekra notes

Paritaprevir + ritonavir + ombitasavir + dasabuvir
Pak: comes with 2 separate tabs (1 taken qam and 1 BID)
XR: 3 tabs daily
both take WITH FOOD
Warning in pts with cirrhosis (liver failure)
3A4 and 2C8 metabolism
women should avoid taking ethinyl estradiol (3A4 inhibition)

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Zepatier notes

elbasvir + grazoprevir
risk of incr LFTs
avoid with strong 3A4 inhibitors
significant drug interaction potential

Common drug interactions with all HCV antivirals

avoid use with strong 3A4 inducers (carbamazepine, phenytoin, rifampin, st johns wort)
Most antivirals incr the levels of statins
Recommend to avoid use with most acid-suppressing agents
Many HIV protease inhibitors
Ethinyl estradiol containing BC

Ribavirin info

inhibits replication of RNA and DNA viruses
used in combo to treat HCV
Virazole: aerosolized used for RSV
teratogenic (most not get pregnant for 6 months after d/c; includ women partners)
SE’s: hemolytic anemia (do not use in unstable CV disease), HA, n/v/d
incr tolerability if taken with food

Interferon alfa info

used for HBV and HCV treatment
regular: SC given 3x/week
pegylated: given weekly
SEs: fatigue, depression, GI upset, incr LFTs, myelosupression
flu-like syndrome (pretreat with APAP and antihistamine)
Very poorly tolerated

Drug class used to treat HBV

NRTI’s

inhibit HBV replication

Boxed warning for all HBV NRTIs

decr dose if crcl < 50
lactic acidosis and severe heptomegaly
exxacerbations of HBV upon d/c

tenofovir notes

disoproxil fumarate (Viread):
300 mg daily
SEs: n/v/d, HA, renal impairment, decr BMD
alafenamide (Vemlidy):
25 mg daily WITH food
less renal impairment and BMD
Can be used in HIV co-infection

Entecavir notes

Baraclude
0.5 mg (treatment naive), 1 mg (resistance)
Take On EMPTY STOMACH
SEs: peripheral edema, ascites, incr LFTs, incr SCr

Other NRTI’s used for HBV

Adefovir (Hepsera)
caution in renal inpairment
Lamivudine (Epivir HBV)
Epivir HBV used for HBV only: 100 mg daily
take 150 mg BID or 300 mg daily if HIV co-infection
Telbivudine (Tyzeka) - can incr CPK

NRTI's that cover HIV and HBV

emtricitabine lamivudine both tenofovir formulations

Cirrhosis

advanced, usually irreversible fibrosis (scarring) of the liver definitively diagnosed via liver biopsy also incr LFTs, decr albumin

Tools used to assess the severity of liver disease

Child-Pugh score (mild, mod, severe) | MELD score

Natural product used for liver disease

Milk thistle | can cause mild diarrhea

Drugs that can cause liver damage

``` APAP (high doses) isoniazid nevirapine NRTIs Tipranavir Valproic acid ```

Most common cause of drug-induced liver injury

alcohol

Drugs used for alcohol dependence

BZDs (for withdrawal) Naltrexone, acamprosate, disulfiram to prevent relapse Support groups vitamins and minerals Vit B1 = prevents (Wernicke-Korsakoff syndrome)

Esophageal varices

caused by a back up blood that cannot easily pass through the liver can be fatal requires surgical intervention if actively bleeding (bands, shunts, etc) Short-term antibiotic prophylaxis is recommended (ceftriaxone/quinolone x 7 days)

Drugs used to vasoconstrict the GI circulation and minimize variceal bleeding:

``` Octreotide (Sandostatin) selective for GI vessels Bolus + continuous infusion x 2-5 days Vasopressin (Vasostrict) non-selective, not 1st line antidiuretic hormone analog ```

Drugs used for primary/secondary prevention of variceal bleeding

``` non-selective beta blockers decr cardiac output (beta-1) decr splanchinic blood flow via vasoconstriction (beta-2) titrate to max dose (HR 55- 60 bpm) Nadolol (Corgard) start at 40 mg QD Propranolol (inderal) start at 20 mg BID ```

Hepatic encephalopathy

symptoms: musty breath odor, confusion, forgetfullness, poor concentration, etc caused by a build-up nitrogenous substances that are usually cleared by the liver (ammonia, etc) Protein intake = 1 - 1.5 g/kg (protein contains Nitrogen)

Drug used for hepatic encephalopathy

Lactulose (1st line): converts ammonia to ammonium =, which can be excreted in feces titrate dose to 2-3 soft bowel movements/day SEs: flatulence, diarrhea, dyspepsia, abd discomfort Antibiotics: Rifaximin (Xifaxan) - 550 mg BID Neomycin Metronidazole (do not use long term)

Ascites

fluid accumulation in the peritoneal cavity restrict sodium intake to < 2g/day Use spironolactone +/- furosemide (lasix ineffective alone) Spironolactone: start 50-100 mg (max 400 mg) preferred ratio: 100 mg spironolactone: 40 mg lasix

Other complications of liver disease

``` Spontaneous Bacterial peritonitis ceftriaxone, quinolones preferred secondary prophylaxis might be needed Hepatorenal syndrome leads to kidney failure albumin, octreotide, midodrine can be used. ```