Viral hepatitis and Drug Induced Liver disease Flashcards
What is inflammation of liver caused by immune respnse called
Acute Viral Hepatitis
What are some symptoms of Acute Viral Hepatitis?
Fatigue, mild fever, nausea, vomiting, diarrhea, anorexia, abdominal pain, dark urine, jaundince
What is Fulminant hepatitis?
Encephalopathy, coagulapathy, cerebral edema and mutliple organ failure (end line of sudden liver inflammation)
Inflammation of the liver and persistently abnormal liver enzymes for at least ____ months is known as ________.
6 months; chronic viral hepatitis
If you have chronic viral hepatitis what are you at risk for involving the liver?
Cirrhosis of the liver and liver cancer
What are some complications of cirrhosis?
portal hypertension, ascites, encephalopathy, variceal bleed, spontaneious bacterial peritonitis, Liver cancer
What is the target organ of injury of hepatitis A virus?
Liver
Who has the highest rates of infection of Hep A and why?
Children, fecal oral route
Is hep A self-limiting or fulminant?
self limiting, only 2% become
Can hep A cause chronic infection?
no
What are some risk factors of hep A?
international travel, sexual/household contaction/ homosexual activity, food or waterborne outbreaks, injection drug use
Does acute hepatitis A have descrete onset of symptoms or does it take a long time?
Discrete
Is there a vaccine for Hep A?
Yes
What is the post exposure tx for Hep A?
Immune Globulin
How soon after infection must immune globulin be given for Hep A? What is the dose and route?
14 days; IM into deltoid or gluteal muscle and its 0.02ml/kg
What is the pre-exposure dose for short and long term?
Short-term: 1-2 months - 0.02ml/kg
long-term: 3-5 months - 0.06ml/kg
What type of virus is Hep B?
Double strand DNA
What are some risk factors for hep B
IVDA, multiple sex partners, inamtes, pregnancy, MSM, high HBV rates, receiving dialysis
What is the tx of hep B for an acute infection?
Supportive therapy
What is the tx for HBV infection for chronic infection?
I LATTE Interferon, Lamivudine, Adefovir, Telbivudine, Tenofovir, Entacavir
What is the end line tx for HBV?
Liver Transplant
What drug tx for HBV is SQ?
IFN
What two drugs are well tolerated side effects?
Lamivudine and Entecavir
What are some benefits of IFN?
no resistance, urable response
What are some negatives of IFN?
many side effects, CI in decompensated liver disease
What is the side effect profile for Lamivudine?
Low
What are some benefits and negatives of Lamivudine?
low cost, well tolerated;
negatives: High resistance
What is a side effect of Adefovir
potential renal toxicity
What is the benefit of Adefovir?
effective when lamivudine resistnace
What are some negatives of Adefovir?
Renal toxicity, slower supporesion
What is the cost like on Adefovir?
Intermediate
What are some side effects of Telbivudine?
Myopathy
What are some benefits of Telbivudine?
More effective than Lamivudine
What are some negatives of Telbivudine?
limited long term, not effective for Lam resistance
What are some side effects of Tenofovir?
dec bone mineral dnsity, renal toxicity
What are some benefits of Tenofovir?
more effective than Adefovir, effective for Lam resistance
What are some negatives of Tenofovir
Decreased bone mineral density and renal toxicity
What are some side effects of Entecavir?
well-tolerated
What are some benefits of Entecavir?
Dec resistance, dec side effects, effective when Lamivudine resistnace
What are some negatives?
limited long term data, high cost
What are the two with renal toxicity?
Adefovir and Tenofovir
What is one side effect of Telbivudine?
Myopathy
What is used for Hep B prevention?
Vaccines: Recombivax HB, Engerix-B, Twinrix (Combination of HAV and HBV)
What populations are indicated for Hep B vaccines
all newborns and adolescents, Healthcare workers, Hemodyalsis pts, increased risk due to sexual practices, post-exposure prophylaxis
What is Hepatitis B Immune Globulin (HBIG) indicated for? What are some brand names?
HepaGamB
HyperHEP B S/D
Nabi-HB
Indicated for passive immunity post exposure prophylaxis and prevention of viral recurrence after liver transplantation
When a pt has muscle pain and renal problems and has tried Lamivudine what anti-viral would you try?
Entecavir
What does all the vaccines have at the end of their name? What about the immune globulin how do you tell those?
X, Its HHN (first letters of all them)
What type of information is in the HCV?
RNA
What is the leading cause of cirrhosis HCC and liver transplantiation?
HCV
What are the three biggest reasons for HCV?
IV Drug Use, Sexual, Tranfusion
What must you do before you tx HCV?
genotype the virus
What is the gold standard of tx for Genotype 1?
pegylated IFN + ribavirin + protease inhibitor
What is the gold standard of tx for Genotype 2,3,4?
peglyated IFN + ribavirin
What are the different types of pegylated interferons?
alfa-2a (pegasys)
alfa-2b (peg-Intron)
What are the two protease inhibitors used for HCV genotype 1 infections?
Telaprevir, boceprevir
What is the end stage of HCV infection?
Liver transplantation
What are some predictors of response?
HCV genotype, baseline viral load, race
What is the dosage and frequency for Pegylated IFNs for HCV infection?
Dosed once weekly: 2a (pegasys) - 180mcg
2b (peg-intron) - weight based
How long to you tx?
based on genotype
What are some adverse effects of Pegylated IFNs?
Fever, chills, HA, myalgia, fatigue, rash, alopcia, retinopath, bone marrow suppression, N/D/V, depression, thyroid disorder
Is Ribavirin effective as monotherapy?
No
What is the preg category of Ribabirin?
X
How many forms of contraception should you use when using Rivavirin?
2 non-estrogen forms
What are some side effects of Ribavirin?
hemolytic anemia (reduce dose), nasal stuffiness, sinusitis, cough, pruritis and rash and fatigue
What is the dose of ribavirin?
depends on genotype and pt weight, reduce dose if hemolytic anemia presents
What type of HCV is protease inhibitors for?
Genotype 1
Is it effective as monotherpay?
no, must be used with Peg-interferon + Ribavirin
What CYP does protease inhibitors act on?
CYP3A4
Regimen and duration of tx based on prior _______. Can you select for resistance in viral infections?
Tx status; yes
What are the two protease inhibitors?
Telaprevir and boceprevir
Can Telaprevir or Boceprevir be used in tx naive, prior relapsers, prior partial or null responders?
Yes
What are the differences in side effects of the two protease inhibitors?
Telaprevir: Rash, pruritis, anemia: BBW of Serious Skin reactions
Boceprevir: anemia, neutropenia, thrombocytopenia
What is the difference in dose of the Protease inhibitors?
Telaprevir: 750mg PO TID
Boceprevir: 300mg PO TID
What is the duration of Tx for genotype 1 HCV?
Peg-interon + Ribavirin + PI = depends onf prior tx
Peg-INF + Ribavirin = 12 months
Peg-INF = 12 months
What is the duration of Tx for genotype 2,3,
Peg-INF + Ribavirin = 6 months
Peg-INF = 12 months
Stop after ____ months of no virologic response
6 months
Early virologic response at ___ and ___ wks predictive of therapy success
4wks and 12 wks
Contraindications to HCV tx?
Pregnancy and 6 months after cessation of therapy, decompensated cirrhosis, uncontrolled depression, active alcohol use or drug abuse, severe leukopeia or thrombocytopenia, uncontrolled thyroid disease, autoimmune disease
What pts does HDV occur in?
HBV pts
Can HBV-HDV be more severe than HBV alone?
Yes
How does you contract HDV?
IVDA or sexual contact
How do you get HEV?
enterically transmitted hepatitis
Is there tx or prevention for HEV?
No
What is the transmission route of HEV?
fecal oral route
How do you manage DILD?
Stop the offending agent
What is the most common cause of acute liver failure?
DILD
WHere is AST found?
Liver and Heart
Where is ALT found?
Liver
Where is AP found?
liver and bone
Where is GGT found
liver and several other organs
What are some acute hepatitis indications or labs?
Jaundice
Serum bilirubin >2x ULN
Serum ALT > 3x ULN (upper limit of normal)
Who is at risk for DILD?
older pts; chronic ingestions of alcohol and acetaminophen and other liver toxic drugs; female gender, familial predispostition
What is the difference between idiosyncratic and intrinsic depatotoxic drug reactions?
Unpredictable vs predictable
Does Acetaminophen have intrinsic hepatotoxicity?
yes (big large single toxic dose)
Which drug has an onset of symptoms as soon as hours to days?
ACetaminophen
How do you diagnose DILD?
rule out other causes of liver injury, examine medication time line
Can you rechallenge someone if they had liver disease?
Yes if u are uncertain about etiology or the medication is essential to well-being of pt
What type of liver damage will be okay to rechallenge a pt in and which will be bad?
Cholestatic is okay but hepatocellular is bad
What is the tx of DILD?
supportive care, remove agent, antidote/protectant, corticosteroids, Ursodiol and referrel for liver transplantation
What is the antidote for APAP overdose?
N-acetylcysteine
What is the toxic dose of APAP in adults and children?
10-15g or 150mg/kg in children leads to hepatic necrosis
How does APAP liver toxicity occur?
APAP metabolized to N-acetyl-p-benzoquinoneimine and gets conjugated with glutathione which causes depletion of glutathion and leads to hepatic necrosis
What pts populations will a lower dose of APAP cause liver damage?
the young and elderly
What effect does 1g QID for 2wks have on your ALT levels?
39% of pts had ALT >3x ULN
Can APAP for long term use cause liver damage and reduce GSH and compromise antioxidant defense capacity?
Yes!!
Who limit APAP to 325mg/tab
FDA
What is the max APAP /day?
4g/day
What is the manufactures max?
3g/day
Is a BBW required on APAP products?
Yes: acetaminophen may cuase severe hepatotoxicity, potentially requiring liver transplant or resulting in death
What is the clinical presentation of APAP hepatotoxicity?
N/V/lethargy, elecated LFTs after 24hrs, jaundice at 72 hours
If ___________ is administers within __ hours after APAP overdose, hepatotoxicity is uncommon.
acetylcysteine; 8 –> be careful of anaphylaxis from acetylcysteine
Can you give it IV or oral?
Yes and Yes