Hepatitis & Liver Disease Flashcards
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
Hepatitis:
inflammation of the liver
-
-
-
- Hepatitis viruses (A, B, C, D, and E), all damage the liver
- alcohol
- drugs
- autoimmune conditions
- other viruses and infections
Treatment of Hepatitis differs depending on the cause of the hepatitis and the extent of the liver damage.
Many patients with hepatitis B and C do not know they are infected.
Transmission occurs primarily via fecal-oral route, due to improper handwashing after exposure to an infected person or ingestion of contaminated food/water.
Hepatitis A virus
Transmission occurs from contact with infectious blood or other bodily fluids, sharing contaminated needles to inject drugs or from an infected mother to her newborn (perinatal transmission).
Hepatitis B and Hepatitis C virus
which hepatitis viruses have a vaccine to prevent from getting?
Hepatitis A (HAV) and Hepatitis B (HBV)
what are those vaccines?
Which hepatitis viruses can cause a chronic infection condition?
Hepatitis B and Hepatitis C (HCV)
- infection can led to fibrosis and scarring of the liver
Which hepatitis viruses can cause an acute infection?
all of them
How do we treat Hepatitis A (HAV)?
HAV only causes an acute self-limited infection.
We treat with only Supportive Care for the patient.
How do we treat Hepatitis B (HBV)?
First line is treated with PEG-INF (pegylated interferon alpha product) OR (NRTI) nucleoside reverse transcriptase inhibitor.
How do we treat Hepatitis C (HCV)?
First line- in a treatment naive patient: DAA (Direct Acting Antiviral) combination
In other select patients:
DAA combination + ribovirin
or
DAA combination + ribovirin + PEG-INF
which vaccine are healthcare providers supposed to receive to protect against which hepatitis virus?
Hepatitis B
PEG-INF is no longer recommended in the guidelines for hepatitis C treatment.
-
-
Drug treatment for (HCV) Hepatitis C virus:
- the virus has 6 different genotypes
- treatment options and duration of therapy depend on genotype
- Is Cirrhosis present?
- Has the patient been treated before?
-
- 2-3 Direct Acting Antivirals (DAAs) with different MOAs
- Duration 12 weeks
Other medications that can be added on: For HCV Tx
- ritonavir (protease inhibitor) = is not active against HCV but is used to boost (increase) levels of HCV protease inhibitors.
- ribavirin
- interferon alpha
If it ends in -previr remember P for PI
NS 3/4A Protease Inhibitors
- grazoprevir
- paritaprevir
- simeprevir
- voxilaprevir
If it ends in -asvir remember A for 5A-RCI
NS 5A Replication Complex Inhibitors
- daclatasvir
- ledipasvir
- ombitasvir
- pibrentasvir
- velpatasvir
If it ends in -buvir remember B for 5B-poly*
NS 5B Polymerase Inhibitor
- dasabuvir
- sofosbuvir
For treatment of HCV in naive patients without cirrhosis, the recommended regimens are:
For ALL (DAAs) Direct Acting Antivirals:
1) Test all patients for HBV before starting a DAA—>
2) For all sofosbuvir containing regimens DO NOT USE with amiodarone–>
Boxed Warning (For ENTIRE CLASS)
* Risk of reactivating HBV; test all patients for HBV before starting a DAA
Warning
sofosbuvir-containing regimens: DO NOT USE amiodarone with sofosbuvir as Serious Symptomatic Bradycardia has been reported.
Side Effects
Well-tolerated; HA, fatigue, diarrhea, nausea
Monitoring
LFTs (including bilirubin), HCV-RNA
which products contain sofosbuvir?
Epclusa
Harvoni
Vosevi
Solvaldi
which products must be dispensed in the original container to protect from moisture?
Epclusa
Harvoni
Vosevi
Solvaldi
“products containing sofosbuvir”
which products are NOT for monotherapy in treating HCV?
(Sovaldi) sofosbuvir, (Olysio) simeprevir, (Daklinza) daclatasvir
- is not effective as monotherapy and is not recommended.
- Should be used with another DAA with different MOA
DAA Drug Interactions:
**ALL DAAs are CONTRAINDICATED with _______________
strong CYP3A4 inducers
remember P’s
(e.g. phenobarbital, phenytoin, rifampin, rifabutin, carbamazepine, oxcarbazepine and St. John’s wort)
DAA Drug Interactions: [Harvoni, Epclusa and Vosevi]
- the sofosbuvir containing products-
Interactions include:
- Antacids, H2RAs and PPI all can decrease concentrations of ledipasvir and velpatasvir
- separate from Antacids by 4 hours
- Take H2RAs at the same time or separated (~12 hours) and use famotidine less than or equal to < 40mg BID or equivalent.
- PPIs are NOT recommended with Epclusa
DAA Drug Interactions:
Ethinyl estradiol-containing products are specifically CONTRAINDICATED with ___________
(Technivie)- ritonavir/ombitasvir/paritaprevir
(Viekira) - a packet containing:
- 2 tablets of [paritaprevir/ritonavir/ombitasvir] &
+ 1 tablet dasabuvir BID
Mavyret
Class:
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MOA:
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Dosing:
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Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
glecaprevir + pibrentasvir
Class:
Indications:
* Approved for Salvage Therapy (failed previous therapy) *
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
-* Approved and used in all 6 different genotypes of HCV for Tx-Naive patients*
-* Approved for 8-week Course Therapy (select patients) *
Drug-Drug/Food interactions:
Epclusa
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
sofosbuvir + velpatasvir
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
**PPIs
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
-* Approved and used in all 6 different genotypes of HCV for Tx-naive patients*
Drug-Drug/Food interactions:
Harvoni
Class:
Indications:
MOA:
Dosage forms:
Dosing:
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Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
sofosbuvir + ledipasvir
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
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Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
Vosevi
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
sofosbuvir + velpatasvir + voxilaprevir
Class:
Indications:
* Approved for Salvage Therapy (failed previous therapy) *
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
Sovaldi
Class:
Indications:
MOA:
Dosage forms:
Dosing:
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Warnings:
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Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
sofosbuvir
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
Viekira Pak
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
paritaprevir + ritonavir + ombitasvir + dasabuvir
Class:
Indications:
MOA:
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Zepatier
Class:
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MOA:
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Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
elbasvir + grazoprevir
Class:
Indications:
MOA:
Dosage forms:
Dosing:
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Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
ribavirin (RBV)
Class:
Indications:
MOA:
Dosage forms:
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Monitoring:
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Drug-Drug/Food interactions:
RIBA
Renal Cl (when CrCl < 50 mL/min)
In combination only
Birth defects.
Anemia: hemolytic (primary toxicity)
Class: antiviral
Indications: (HCV) Hepatitis C Virus
MOA: is an oral antiviral drug that inhibits replication of RNA and DNA viruses.
Dosage forms: capsule, tablet
Dosing: 400-600mg BID, varies based on indication, patient weight and genotype.
Max dose:
Boxed Warning:
Pregnancy Category X: significant teratogenic effects, even in female partners of male patients taking the medication.
**hemolytic anemia (primary toxicity of oral therapy, mostly occurring within 1-2 weeks of initiation) **
Contraindications:
- if renal CrCl is less than < 50mL/min
Warnings:
Side Effects:
Monitoring:
– if Hgb is less < 10g/dL: reduce dose
–** if Hgb is less than < 8.5 g/dL, then AVOID USE**
Pearls/Notes:
- used in combination with other drugs, NOT for monotherapy
- Pregnancy Category X: Avoid pregnancy during therapy and for 6 months after completion of therapy; Use 2 forms of birth control
- increased tolerability if given with food
- capsule should NOT be crushed, chewed, opened or broken
Drug-Drug/Food interactions:
- zidovudine can increase risk and severity of anemia from ribavirin
- Do NOT use with didanosine(Videx) due to cases of fatal hepatic failure, peripheral neuropathy and pancreatitis.
PegIntron
Pegasys
“pegylated forms”
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
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Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
pegylated-Interferon alfa (PEG-INF-ALFA)
Class:
Indications:
- is approved for the treatment of (HBV) hepatitis B virus as monotherapy.
- is approved for the treatment of (HCV) hepatitis C virus
- some cancers
MOA:
- interferons are naturally produced cytokines that have antiviral, antiproliferative and immunomodulatory effects. The pegylated forms (PEG-INF-alfa) have polyethylene glycol added, which prolongs the half-life, reducing the dosing to once weekly.
Dosage forms:
Dosing:
SC dosing varies by indication and products:
once weekly for (Pegasys, PegIntron)
three times weekly for Intron A
Max dose:
Boxed Warnings:
Can cause or exacerbate: neuropsychiatric, autoimmune, ischemic or infectious disorders; if used with ribavirin, teratogenic/anemia risk.
Contraindications:
Autoimmune hepatitis, decompensated liver disease in cirrhotic patients, infants/neonates (Pegasys).
Warnings:
Neuropsychiatric events, cardiovascular events, endocrine disorders
Side Effects:
- CNS effects (fatigue, depression, anxiety, weakness), GI upset, increased LFTs (5-10 x ULN during treatment), myelosuppression, mild alopecia.
- Flu-like syndrome 1-2 hours after administration (fever, chills, HA, malaise); pre-treat with acetaminophen and an antihistamine.
Monitoring:
Pearls/Notes:
-HCV guidelines DO NOT recommend interferon products, but they will continue to be used when other treatments are contraindicated or too costly.
- Interferons have toxicities and lab abnormalities that limit their use.
- Stop Tx or reduce dose based on: ANC, platelets and CrCl
- Interferons do NOT provide a cure and are hard to take/tolerate
Drug-Drug/Food interactions:
Interferon-Beta:
Is for the treatment of ___________
(MS) Multiple Sclerosis
Treatment for Hepatitis B (HBV):
tenofovir -nof
Nephrotoxic
Osteoporosis
Fanconi syndrome
Preferred monotherapy NRTIs in the Tx of (HBV):
tenofovir disoproxil fumarate (TDF) - Viread
tenofovir alafenamide (TAF) - Vemlidy
entecavir (Baraclude)
For ALL HBV NRTIs:
If CrCl is less than < 50 mL/min: then decrease dose or frequency
Exception- Vemlidy
Boxed Warnings:
-* Lactic acidosis and severe hepatomegaly with stenosis, which can be fatal*
-* Exacerbations of HBV can occur upon discontinuation, monitor closely
-* Can cause HIV resistance in HBV patients with unrecognized or untreated HIV infection.*
Viread
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
tenofovir disoproxil fumarate (TDF)
Class: Antiviral
(NRTIs) Nucleoside Reverse Transcriptase Inhibitors
Indications:
- approved for (HBV) Hepatitis B virus treatment as monotherapy**
MOA:
- drug inhibits HBV replication by inhibiting HBV polymerase resulting in DNA chain termination.
Dosage forms: tablet, powder (oral)
Dosing:
300mg daily
Max dose:
Boxed Warnings:
-* Lactic acidosis and severe hepatomegaly with stenosis, which can be fatal*
-* Exacerbations of HBV can occur upon discontinuation, monitor closely
-* Can cause HIV resistance in HBV patients with unrecognized or untreated HIV infection.*
Contraindications:
Warnings:
-Renal toxicity including acute renal failure and/or Fanconi syndrome, osteomalacia, and decreased bone mineral density.
Side Effects:
GI upset, rash, increased LFTs, N/V/D, *decreased bone mineral density, *renal impairment, increased CPK, HA
Monitoring:
-* if CrCl is less than < 50 mL/min: then decrease dose or frequency*.
Pearls/Notes:
- Preferred therapy
-
- Prior to starting HBV therapy, all patients should be tested for HIV
- Antivirals used for HBV can have activity against HIV, and if a patient is co-infected with both HIV and HBV, it is important that the chosen therapy is appropriate for both viruses to MINIMIZE risk of HIV antiviral resistance
Drug-Drug/Food interactions:
- **tenofovir formulations: Do NOT use with adefovir due to increased risk of virologic failure and potential for increased side effects.
Vemlidy
-lidy
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
tenofovir alafenamide (TAF)
Class: Antiviral
(NRTIs) Nucleoside Reverse Transcriptase Inhibitors
Indications:
- approved for (HBV) Hepatitis B virus treatment as monotherapy**
MOA:
- drug inhibits HBV replication by inhibiting HBV polymerase resulting in DNA chain termination.
Dosage forms: tablet
Dosing:
25mg daily with food
Max dose:
Boxed Warnings:
-* Lactic acidosis and severe hepatomegaly with stenosis, which can be fatal*
-* Exacerbations of HBV can occur upon discontinuation, monitor closely
-* Can cause HIV resistance in HBV patients with unrecognized or untreated HIV infection.*
Contraindications:
Warnings:
-Renal toxicity including acute renal failure and/or Fanconi syndrome, osteomalacia, and decreased bone mineral density.
Side Effects:
- GI upset, rash, increased LFTs
-* Nausea, headache, abdominal pain, fatigue, cough, decreased bone mineral density
Monitoring:
-*if CrCl is less than < 15mL/min: NOT recommended
Pearls/Notes:
- Preferred therapy*
-*protect from moisture; *Dispense only in original container**
- Prior to starting HBV therapy, all patients should be tested for HIV
- Antivirals used for HBV can have activity against HIV, and if a patient is co-infected with both HIV and HBV, it is important that the chosen therapy is appropriate for both viruses to MINIMIZE risk of HIV antiviral resistance
- *Is associated with decreased renal and bone toxicity compared to TDF
- *Is a substrate for P-gp**:
Drug-Drug/Food interactions:
Do NOT Use with adefovir due to increased risk of virologic failure and potential for increased side effects.
- adefovir
- oxcarbazepine, phenytoin, phenobarbital, rifampin and St. John’s wort
(TAF) tenofovir alafenamide is a substrate for ___________.
So do NOT use with _______.
P-gp
oxcarbazepine, phenytoin, phenobarbital, rifampin and St. John’s wort
Baraclude
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
entecavir
Class: Antiviral
(NRTIs) Nucleoside Reverse Transcriptase Inhibitors
Indications:
- approved for (HBV) Hepatitis B virus treatment as monotherapy**
MOA:
- drug inhibits HBV replication by inhibiting HBV polymerase resulting in DNA chain termination.
Dosage forms: tablet, oral solution
Dosing:
Take on an empty stomach
Nucleoside-Tx naive: 0.5mg daily
If Lamivudine-resistant: 1mg daily
Max dose:
Boxed Warnings:
-* Lactic acidosis and severe hepatomegaly with stenosis, which can be fatal*
-* Exacerbations of HBV can occur upon discontinuation, monitor closely
-* Can cause HIV resistance in HBV patients with unrecognized or untreated HIV infection.*
Contraindications:
Warnings:
Side Effects:
GI upset, rash, increased LFTs
- peripheral edema, pyrexia(fever), ascites, hematuria
Monitoring:
-* if CrCl is less than < 50 mL/min: then decrease dose or frequency*.
Pearls/Notes:
- Preferred therapy*
- Food reduces AUC by 18-20%; Take on an empty stomach (2 hours before or after a meal)
- Prior to starting HBV therapy, all patients should be tested for HIV
- Antivirals used for HBV can have activity against HIV, and if a patient is co-infected with both HIV and HBV, it is important that the chosen therapy is appropriate for both viruses to MINIMIZE risk of HIV antiviral resistance
Drug-Drug/Food interactions:
Epivir HBV
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
lamivudine
Class: Antiviral
(NRTIs) Nucleoside Reverse Transcriptase Inhibitors
Indications:
- approved for (HBV) Hepatitis B virus treatment as monotherapy**
MOA:
- drug inhibits HBV replication by inhibiting HBV polymerase resulting in DNA chain termination.
Dosage forms: tablet, oral solution
Dosing:
100mg daily
150mg BID or 300mg daily if co-infected with HIV
Max dose:
Boxed Warnings:
-* Lactic acidosis and severe hepatomegaly with stenosis, which can be fatal*
-* Exacerbations of HBV can occur upon discontinuation, monitor closely
-* Can cause HIV resistance in HBV patients with unrecognized or untreated HIV infection.*
-**Do NOT Use Epivir-HBV for the treatment of HIV (contains lower dose of lamivudine); can result in HIV resistance.
Contraindications:
Warnings:
Side Effects:
GI upset, rash, increased LFTs
headache, N/V/D, fatigue, insomnia, myalgias, increased LFTs, pancreatitis (rare)
Monitoring:
-* if CrCl is less than < 50 mL/min: then decrease dose or frequency*.
Pearls/Notes:
- Prior to starting HBV therapy, all patients should be tested for HIV
- Antivirals used for HBV can have activity against HIV, and if a patient is co-infected with both HIV and HBV, it is important that the chosen therapy is appropriate for both viruses to MINIMIZE risk of HIV antiviral resistance
Drug-Drug/Food interactions:
- Bactrim (SMX/TMP) can increase lamivudine levels due to decreased excretion.
Hepsera
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
adefovir
Class: Antiviral
(NRTIs) Nucleoside Reverse Transcriptase Inhibitors
Indications:
- approved for (HBV) Hepatitis B virus treatment as monotherapy**
MOA:
- drug inhibits HBV replication by inhibiting HBV polymerase resulting in DNA chain termination.
Dosage forms:
Dosing:
10mg daily
Max dose:
Boxed Warnings:
-* Lactic acidosis and severe hepatomegaly with stenosis, which can be fatal*
-* Exacerbations of HBV can occur upon discontinuation, monitor closely
-* Can cause HIV resistance in HBV patients with unrecognized or untreated HIV infection.*
-**Caution in patients with renal impairment of those at risk of renal toxicity (including concurrent nephrotoxic drugs or NSAIDs)
Contraindications:
Warnings:
Side Effects:
GI upset, rash, increased LFTs
HA, weakness, abdominal pain, hematuria, rash,
Monitoring:
-* if CrCl is less than < 50 mL/min: then decrease dose or frequency*.
Pearls/Notes:
- Prior to starting HBV therapy, all patients should be tested for HIV
- Antivirals used for HBV can have activity against HIV, and if a patient is co-infected with both HIV and HBV, it is important that the chosen therapy is appropriate for both viruses to MINIMIZE risk of HIV antiviral resistance
Drug-Drug/Food interactions:
T-TEAL “the 5 drugs approved for treatment of HBV:
tenofovir disoproxil fumarate (Viread)
tenofovir alafenamide (Vemlidy)
entecavir (Baraclude)
adefovir (Hepsera)
lamivudine (Epivir HBV)
Cirrhosis:
is advanced fibrosis (scarring) of the liver that is usually irreversible.
- As scar tissue replaces healthy liver tissue, blood flow through the liver is impaired, leading to numerous complications including portal hypertension, gastroesophageal varices, ascites and hepatic encephalopathy.
There are many causes for cirrhosis, the most common in the US are ____________
HCV and alcohol
symptoms/clinical presentation of Cirrhosis and/or later stages of liver disease:
Pathology:
- remember the common bile duct sits closely to the liver next to the hepatic artery & portal vein. So, a lot can potentially be affected if the liver gets diseased and damaged.
- nausea/vomiting/diarrhea
- loss of appetite
- malaise/fatigue
- pain in the upper right quadrant of the abdomen
-* yellowed skin
-* yellowed whites of the eyes (jaundice) and darkened urine - stool can become lighter in color (white or clay colored), due to decreased bile (from decreased production or blocked bile duct).
Cirrhosis diagnosis:
Objective Criteria:
Increased [ AST/ALT/Alk Phos/ TBili/LDH/PT/INR]
Decreased [albumin/platelets]
- with a liver biopsy
” however, certain lab results can suggest cirrhosis or other typer of liver damage”
-LFT: Liver function tests:
Increase
Normal reference range for (AST) aspartate aminotransferase:
10-40 units/L
- in general, the higher the values the more active (acute) the liver disease or inflammation
Normal reference range for (ALT) alanine aminotransferase:
10-40 units/L
- in general, the higher the values the more active (acute) the liver disease or inflammation
Normal reference range for albumin:
3.5-5.5 g/dL
- protein produced by the liver
Normal reference range for (TBili) total Bilirubin:
0.1-1.2 mg/dL
- used along with other liver tests to determine causes of liver damage and detect bile duct blockage.
Normal reference range for platelets:
150000-450000 cells/mm^3
Normal reference range for (PT) Prothrombin Time / (INR) International Normalized Ratio:
PT: 10-13 seconds (varies)
INR: < 1.2 (for those not on warfarin)
Albumin and PT/INR are markers of _____________ AND are likely to be altered in chronic liver disease (particularly cirrhosis).
synthetic liver function (production ability)
A hepatic panel also called (LFT) Liver Function Test:
comprises of (AST, ALT, TBili, and Alk Phos) is used to _______________________________________________________________
-assess acute and chronic liver inflammation/disease, and for baseline and routine monitoring of hepatotoxic drugs.
Liver disease
when a patients liver enzymes begin to normalize, lab values that go unchanged would be INR and albumin.
patient will always have a high INR and a low albumin. This indicates to use that the patients liver is not working properly.
- both are made in the liver
Assessing Severeity of Liver Disease:
” a couple different classification systems”, these include:
____________ and ____________
- The severity of liver disease serves as a predictor of patient survival, surgical outcomes and the risks of complications, such as variceal bleeding.
1) Child-Pugh Classification: [also called The Child-Turcotte-Pugh (CTP) Classification System]
- - - the higher the score the more severe the liver disease
- - - score ranges from 0 - 15
2) Model for End Stage Liver Disease (MELD)
- - a score ranging from 0 - 40
- - higher number indicates a greater risk of death within 3 months
- - used most for determining someone’s eligibility for liver transplant
Child-Pugh Classification:
A score of _________ would indicate mild disease or Class A
a score of less than < 7
Child-Pugh Classification:
A score of _______ would indicate moderate disease or Class B
a score of 7-9
Child-Pugh Classification:
A score of ________ would indicate severe liver disease or Class C
a score of 10-15
Natural Products:
Milk Thistle, an extract derived from a member of the daisy family, is sometimes used by patients with liver disease.
______ and _________ are known hepatotoxins
Kava
flavocoxid
(DILI) Drug-Induced Liver Injury
LiverTox website
- gives information of drugs that have an association on drug induced liver disease
Lab Tests For Liver Disease:
- Specific LFT abnormalities can help distinguish between types of liver disease.
Lab Tests For Liver Disease:
- Specific LFT abnormalities can help distinguish between types of liver disease.
Acute Liver toxicity, including from drugs:
- Increased AST/ALT
Lab Tests For Liver Disease:
- Specific LFT abnormalities can help distinguish between types of liver disease.
Chronic liver disease (e.g. cirrhosis):
- Increased AST/ALT, Alk Phos, TBili, LDH, PT/INR
- Decreased Albumin
Lab Tests For Liver Disease:
- Specific LFT abnormalities can help distinguish between types of liver disease.
Alcoholic Liver Disease:
Increased AST greater than > ALT, (AST will be about double the ALT), increased gamma glutamyl transpeptidase (GGT)
Lab Tests For Liver Disease:
- Specific LFT abnormalities can help distinguish between types of liver disease.
Hepatic encephalopathy:
increased ammonia
normal reference range for ammonia (19-60 mcg/dL)
Lab Tests For Liver Disease:
- Specific LFT abnormalities can help distinguish between types of liver disease.
Jaundice
Increased TBili
normal reference range for TBili: 0.1-1.2 mg/dL
Hepatotoxic drugs are typically discontinued when the LFTs are _______________
greater than > 3 times the upper limit of normal (ULN) - - (> 150 units/L of ALT or AST)
Select Drugs with a BOXED WARNING for LIVER DAMAGE:
-
- acetaminophen (high doses, acute or chronic), amiodarone
- isoniazid
- ketoconazole (oral)
- methotrexate
- nefazodone
- nevirapine
- NRTIs
- Propylthiouracil
- Tipranavir
- Valproic acid
Alcoholic Liver Disease (ALD):
- the most common type of drug induced liver disease.
- women have a higher risk than men.
- risk increases with duration and amount of alcohol consumed.
- ALD can include fatty liver, alcoholic hepatitis and chronic hepatitis with fibrosis or cirrhosis.
Treatment of (ALD) Alcoholic Liver Disease:
The most important part of treatment is ______1______
Proper Nutrition is essential to help the liver recover. ____2______ is used to prevent and treat Wernicke-Korsakoff syndrome.
1- Alcohol cessation
2- Thiamine (vitamin B1)
Wernicke’s encephalopathy and Korsakoff syndrome are different conditions that are both due to brain damage caused by a lack of _____________.
vitamin B1
Treatment programs primarily use __________ for alcohol withdrawal in inpatients.
benzodiazepines
Drugs used to prevent relapses include:
Naltrexone (Vivitrol)
acamprosate
disulfiram (Antabuse)
Complications with Liver Disease and Cirrhosis:
Portal hypertension & Variceal bleeding
- portal hypertension: increased blood pressure in the portal vein. This can cause complications, including the development of esophageal varices (enlarged veins in the lower part of the esophagus).
-
- when blood flow through the liver is blocked by scar tissue, it backs up and flows into smaller blood vessels. These vessels can balloon out and bleed if they break open (Variceal bleeding).
-
Hepatic Encephalopathy
-
Ascites
-
(SBP) Spontaneous Bacterial Peritonitis
-
Hepatorenal Syndrome
-
Complications with Liver Disease and Cirrhosis:
Acute Treatment of Variceal bleeding:
What agents do we use to stop or minimize the bleeding? How do they do this?
octreotide or vasopressin
- medications that vasoconstrict the splanchnic (GI) circulation can stop or minimize the bleeding.
Octreotide (selective for splanchnic vessels)
Vasopressin (non-selective)
Complications with Liver Disease and Cirrhosis:
Treatment of variceal bleeding:
Band ligation-1
or
sclerotherapy-2
1) putting a band around the vessel
2) injecting a solution into the vessel to make it collapse and close
“are recommended first-line treatments for bleeding varices”
Complications with Liver Disease and Cirrhosis:
Prevention (primary and secondary) of variceal bleeding:
What agents do we use to prevent future bleeds from happening or reoccurrence after a patient has survived? what mechanism do they work by?
non-selective beta blockers:
- nadolol (Corgard) (convenient because can be given once a day)
- propranolol (Inderal LA, Inderal XL)
[when starting these drugs for a patient to be on indefinitely, the target heart rate HR we want is ~55-60 BPM]
they reduce portal pressure by reducing portal venous inflow through 2 ways:
1) decreasing cardiac output (via beta-1)
2) decreasing splanchnic blood flow due to vasoconstriction (via beta-2 and unopposed alpha activity)
Complications with Liver Disease and Cirrhosis:
Hepatic Encephalopathy:
1) Symptoms include:
2) Why does it occur?
3) How do we Treat:
- anyone with liver disease can experience hepatic encephalopathy.
1) - musty odor of the breath and/or urine
- changes in thinking
- confusion
- forgetfulness
- drowsiness
- disorientation
- mood changes
- poor concentration
- hand tremor (asterixis)- inability to maintain sustained posture
2) There is accumulation of waste products. Ammonia (NH3) being the big culprit.
3) Lactulose -> to help us reduce the ammonia levels in the blood and treat hepatic encephalopathy.
“Lactulose is also used for constipation, this helps the patient have a bowel movement, which is good. This is getting rid of the ammonia.”
-
-
- Most patients that have had hepatic encephalopathy, will need to be on something to treat it and prevent it for the rest of their lives.
Complications with Liver Disease and Cirrhosis:
Ascites:
What is it?
How do we treat?
Ascites: is fluid accumulation within the peritoneal space.
“this can lead to the development of (SPB) and (HRS)”
Diuretics- in particular a (K) potassium sparing diuretic and an aldosterone antagonist.
orally we use: Spironolactone 100mg + furosemide 40mg ratio
titrating up
Complications with Liver Disease and Cirrhosis:
Ascites:
If patient is very short of breath and sometimes getting the fluid off with diuretics alone is very hard.
Another approach we may have to use that’s invasive is __________
paracentesis
Complications with Liver Disease and Cirrhosis:
(SBP) Spontaneous Bacterial Peritonitis:
What is it?
How do we treat?
- with all the fluid buildup accumulating in the abdomen (ascites). This fluid can get infected.
- the infection can seed from other places in the GI tract.
Generally providing coverage for streptococcus and enteric gram (-) negative pathogens.
we use Ceftriaxone (or an equivalent) for 5-7 days is recommended.
Complications with Liver Disease and Cirrhosis:
Hepatorenal Syndrome (HRS):
What is it?
How do we treat?
Sandostatin
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
octreotide
Class: somatostatin analog
Indications: bleeding varices
MOA: drug is SELECTIVE for splanchnic vessels and causes vasoconstriction to stop or minimize the bleeding.
Dosage forms:
Dosing:
Bolus: 25-100 mcg IV (usual 50mcg) can repeat in 1 hour if hemorrhage not controlled.
Continuous infusion: 25-50 mcg/hr x 2-5 days
Max dose:
Contraindications:
Warnings:
Side Effects:
*Bradycardia, cholelithiasis, biliary sludge, chest pain, fatigue, HA, pruritus, hyperglycemia,
Monitoring:
blood glucose, HR, ECG
Pearls/Notes:
Drug-Drug/Food interactions:
Vasostrict
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
vasopressin
Class: Antidiuretic hormone analog (
Indications:
NOT 1st line (usually used with nitroglycerin IV to prevent myocardial infarction)
MOA: drug is NON-selective and causes vessels around the GI to vasoconstrict.
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
arrhythmias, chest pain, MI, decreases cardiac output, increases blood pressure, N/V
Monitoring:
BP, HR, ECG, fluid balance
Pearls/Notes:
Drug-Drug/Food interactions:
Corgard
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
nadolol
Class: NON-selective beta-blocker
Indications: primary and secondary prevention of variceal bleeding.
MOA: drug reduces portal pressure by reducing portal venous inflow, through 2 mechanisms:
1) decreasing cardiac output (via beta-1 blockade)
2) decreasing splanchnic blood flow due to vasoconstriction (via beta-2 blockade & unopposed alpha activity)
Dosage forms:
Dosing:
Initial: 40mg PO daily
Max dose:
Boxed Warning:
**Do not withdraw beta-blockers abruptly (particularly in patients with CAD), gradually taper over 1-2 weeks to avoid acute tachycardia, HTN and/or ischemia. **
Contraindications:
*Sinus bradycardia, 2nd or 3rd degree heart block, sick sinus syndrome (unless patient has a functioning artificial pacemaker) or cardiogenic shock; Do NOT initiate in patients with an active asthma exacerbation.
Warnings:
NON-selective drugs are used for PORTAL HYPERTENSION; use extreme caution with asthma, severe COPD, peripheral vascular disease or Raynaud’s disease (a condition with vasospasms in the extremities)
- Can mask signs of hyperthyroidism and aggravate psychiatric conditions; use caution in patients with diabetes (particularly with recurrent hypoglycemia) **
Side Effects:
Monitoring:
HR, BP
Pearls/Notes:
- beta-blocker is titrated to the maximal tolerated dose (target HR 55-60 BPM) and continued indefinitely.
Drug-Drug/Food interactions:
Inderal LA
Inderal XL
InnoPran XL
Hemangeol
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
propranolol
Class: NON-selective beta-blocker
Indications: primary and secondary prevention of variceal bleeding.
MOA: drug reduces portal pressure by reducing portal venous inflow, through 2 mechanisms:
1) decreasing cardiac output (via beta-1 blockade)
2) decreasing splanchnic blood flow due to vasoconstriction (via beta-2 blockade & unopposed alpha activity)
Dosage forms:
Dosing:
Initial: 20mg PO BID
Max dose:
Boxed Warning:
**Do not withdraw beta-blockers abruptly (particularly in patients with CAD), gradually taper over 1-2 weeks to avoid acute tachycardia, HTN and/or ischemia. **
Contraindications:
*Sinus bradycardia, 2nd or 3rd degree heart block, sick sinus syndrome (unless patient has a functioning artificial pacemaker) or cardiogenic shock; Do NOT initiate in patients with an active asthma exacerbation.
Warnings:
NON-selective drugs are used for PORTAL HYPERTENSION; use extreme caution with asthma, severe COPD, peripheral vascular disease or Raynaud’s disease (a condition with vasospasms in the extremities)
- Can mask signs of hyperthyroidism and aggravate psychiatric conditions; use caution in patients with diabetes (particularly with recurrent hypoglycemia) **
Side Effects:
Monitoring:
HR, BP
Pearls/Notes:
- beta-blocker is titrated to the maximal tolerated dose (target HR 55-60 BPM) and continued indefinitely.
Drug-Drug/Food interactions:
Enulose
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
lactulose
Class: nonabsorbable disaccharides, laxative osmotic, ammonium detoxicant.
Indications: first line for acute and chronic prevention and treatment of hepatic encephalopathy.
MOA:
drug works by converting ammonia (NH3) produced by intestinal bacteria to ammonium (NH4), which is polar and therefore cannot readily diffuse into the blood. lactulose enhances diffusion of ammonia into the colon for excretion. This helps get it excreted into the stool and out of the body.
Dosage forms: oral solution and packet
Dosing:
Treatment: 30-45mL (or 20-30 grams) PO every hour until stool evacuation; then 30-45mL (20-30 grams) PO 3-4 times/day, titrated to produce 2-3 soft bowel movements daily.
Enema: Q4-6 hours as needed
Prevention: 30-45mL (or 20-30 grams) PO 3-4 times/day, titrated to produce 2-3 soft bowel movements daily.
Max dose:
Contraindications:
Low galactose diet
Warnings:
Side Effects:
flatulence, diarrhea, dyspepsia, abdominal discomfort, dehydration, hypernatremia
Monitoring:
*mental status, *bowel movements, *ammonia, fluid status, electrolytes.
Pearls/Notes:
Drug-Drug/Food interactions:
Constulose
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
lactulose
Class: nonabsorbable disaccharides, laxative osmotic, ammonium detoxicant.
Indications: first line for acute and chronic prevention and treatment of hepatic encephalopathy.
MOA:
drug works by converting ammonia (NH3) produced by intestinal bacteria to ammonium (NH4), which is polar and therefore cannot readily diffuse into the blood. This helps get it excreted into the stool and out of the body.
Dosage forms: oral solution and packet
Dosing:
Treatment: 30-45mL (or 20-30 grams) PO every hour until stool evacuation; then 30-45mL (20-30 grams) PO 3-4 times/day, titrated to produce 2-3 soft bowel movements daily.
Enema: Q4-6 hours as needed
Prevention: 30-45mL (or 20-30 grams) PO 3-4 times/day, titrated to produce 2-3 soft bowel movements daily.
Max dose:
Contraindications:
Low galactose diet
Warnings:
Side Effects:
flatulence, diarrhea, dyspepsia, abdominal discomfort, dehydration, hypernatremia
Monitoring:
*mental status, *bowel movements, *ammonia, fluid status, electrolytes.
Pearls/Notes:
Drug-Drug/Food interactions:
Kristalose
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
lactulose
Class: nonabsorbable disaccharides, laxative osmotic, ammonium detoxicant.
Indications: first line for acute and chronic prevention and treatment of hepatic encephalopathy.
MOA:
drug works by converting ammonia (NH3) produced by intestinal bacteria to ammonium (NH4), which is polar and therefore cannot readily diffuse into the blood. This helps get it excreted into the stool and out of the body.
Dosage forms: oral solution and packet
Dosing:
Treatment: 30-45mL (or 20-30 grams) PO every hour until stool evacuation; then 30-45mL (20-30 grams) PO 3-4 times/day, titrated to produce 2-3 soft bowel movements daily.
Enema: Q4-6 hours as needed
Prevention: 30-45mL (or 20-30 grams) PO 3-4 times/day, titrated to produce 2-3 soft bowel movements daily.
Max dose:
Contraindications:
Low galactose diet
Warnings:
Side Effects:
flatulence, diarrhea, dyspepsia, abdominal discomfort, dehydration, hypernatremia
Monitoring:
*mental status, *bowel movements, *ammonia, fluid status, electrolytes.
Pearls/Notes:
Drug-Drug/Food interactions:
Generlac
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
lactulose
Class: nonabsorbable disaccharides, laxative osmotic, ammonium detoxicant.
Indications: first line for acute and chronic prevention and treatment of hepatic encephalopathy.
MOA:
drug works by converting ammonia (NH3) produced by intestinal bacteria to ammonium (NH4), which is polar and therefore cannot readily diffuse into the blood. This helps get it excreted into the stool and out of the body.
Dosage forms: oral solution and packet
Dosing:
Treatment: 30-45mL (or 20-30 grams) PO every hour until stool evacuation; then 30-45mL (20-30 grams) PO 3-4 times/day, titrated to produce 2-3 soft bowel movements daily.
Enema: Q4-6 hours as needed
Prevention: 30-45mL (or 20-30 grams) PO 3-4 times/day, titrated to produce 2-3 soft bowel movements daily.
Max dose:
Contraindications:
Low galactose diet
Warnings:
Side Effects:
flatulence, diarrhea, dyspepsia, abdominal discomfort, dehydration, hypernatremia
Monitoring:
*mental status, *bowel movements, *ammonia, fluid status, electrolytes.
Pearls/Notes:
Drug-Drug/Food interactions:
Xifaxan
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
rifaximin
Class: antibiotic
Indications:
preferred 2nd line Tx of Hepatic encephalopathy.
MOA: drug works by inhibiting the activity of urease-producing bacteria, which decreases ammonia production.
Dosage forms: tablet
Dosing:
Prevention: 550mg PO BID
Treatment (Off-label): 400mg PO every 8 hours x5-10 days
Max dose:
Contraindications:
Warnings:
Side Effects: peripheral edema, dizziness, fatigue, nausea, ascites, flatulence, headache
Monitoring:
mental status, ammonia
Pearls/Notes:
Drug-Drug/Food interactions:
neomycin
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
Class: antibiotic
Indications: (HE) hepatic encephalopathy
MOA:
Dosage forms:
Dosing:
4-12 grams daily divided every 4-6 hours x 5-6 days
Max dose:
Boxed Warnings:
**neurotoxicity (hearing loss, vertigo, ataxia-impaired coordination); nephrotoxicity (particularly in renal impairment or with concurrent use of other nephrotoxic drugs);
- can cause neuromuscular blockade and respiratory paralysis especially when given soon after anesthesia or with muscle relaxants.
Contraindications:
Warnings:
Side Effects:
*GI upset, ototoxicity, nephrotoxicity, irritation/soreness of mouth/rectal area
Monitoring:
Mental status, renal function, hearing, ammonia
Pearls/Notes:
Drug-Drug/Food interactions:
Flagyl
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
metronidazole
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
- Do not use long term due to peripheral neuropathies**
Drug-Drug/Food interactions:
Patients with ascites due to portal hypertension should:
- restrict dietary sodium intake _________
- avoid sodium retaining medications (including _______)
- use diuretics to increase fluid loss
- Restriction of fluid is recommended only in patient with symptomatic severe hyponatremia (________________)
- to < 2 grams/day
- ## NSAIDs
- serum Na less than < 120mEq/L
Diuretic therapy for ascites can be initiated with either:
1)
or
2)
Spironolactone monotherapy
or
Spironolactone + furosemide
___________ by itself is ineffective.
furosemide
Spironolactone is initiated at a dose of _______1______ and increased to a maximum dose of ______2______ per day.
1) 50-100mg
2) 400mg
When used in combination, spironolactone and furosemide, if possible, a ratio of _______________ to ___________ should be used to maintain potassium balance.
40mg furosemide
100mg spironolactone
The spironolactone oral suspension (CaroSpir) is NOT therapeutically equivalent to oral tablets (Aldactone).
The approved CaroSpir dose for treating edema associated with cirrhosis is ___________ in single or divided doses.
20-75mg (4-15 mL)
In Severe cases of ascites, abdominal paracentesis is needed to directly remove ascitic fluid.
Large volume paracentesis (removal of greater than > 5L) is associated with significant fluid shifts and the addition of albumin (_________________) is recommended to prevent paracentesis-induced circulatory dysfunction AND progression to hepatorenal syndrome.
6-8 grams per liter of fluid removed.
spironolactone
furosemide
