Hepatitis & Liver Disease

Question 1

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Question 2

Hepatitis:

Answer 2

inflammation of the liver

Question 3

-
-
-

Answer 3

• Hepatitis viruses (A, B, C, D, and E), all damage the liver
• alcohol
• drugs
• autoimmune conditions
• other viruses and infections

Question 4

Treatment of Hepatitis differs depending on the cause of the hepatitis and the extent of the liver damage.

Answer 4

Many patients with hepatitis B and C do not know they are infected.

Question 5

Transmission occurs primarily via fecal-oral route, due to improper handwashing after exposure to an infected person or ingestion of contaminated food/water.

Answer 5

Hepatitis A virus

Question 6

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).

Answer 6

Hepatitis B and Hepatitis C virus

Question 7

which hepatitis viruses have a vaccine to prevent from getting?

Answer 7

Hepatitis A (HAV) and Hepatitis B (HBV)

what are those vaccines?

Question 8

Which hepatitis viruses can cause a chronic infection condition?

Answer 8

Hepatitis B and Hepatitis C (HCV)

• infection can led to fibrosis and scarring of the liver

Question 9

Which hepatitis viruses can cause an acute infection?

Answer 9

all of them

Question 10

How do we treat Hepatitis A (HAV)?

Answer 10

HAV only causes an acute self-limited infection.

We treat with only Supportive Care for the patient.

Question 11

How do we treat Hepatitis B (HBV)?

Answer 11

First line is treated with PEG-INF (pegylated interferon alpha product) OR (NRTI) nucleoside reverse transcriptase inhibitor.

Question 12

How do we treat Hepatitis C (HCV)?

Answer 12

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

Question 13

which vaccine are healthcare providers supposed to receive to protect against which hepatitis virus?

Answer 13

Hepatitis B

Question 14

PEG-INF is no longer recommended in the guidelines for hepatitis C treatment.

Answer 14

-
-

Question 15

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?

-

Answer 15

• 2-3 Direct Acting Antivirals (DAAs) with different MOAs
• Duration 12 weeks

Question 16

Other medications that can be added on: For HCV Tx

Answer 16

• ritonavir (protease inhibitor) = is not active against HCV but is used to boost (increase) levels of HCV protease inhibitors.
• ribavirin
• interferon alpha

Question 17

If it ends in -previr remember P for PI

Answer 17

NS 3/4A Protease Inhibitors

• grazoprevir
• paritaprevir
• simeprevir
• voxilaprevir

Question 18

If it ends in -asvir remember A for 5A-RCI

Answer 18

NS 5A Replication Complex Inhibitors

• daclatasvir
• ledipasvir
• ombitasvir
• pibrentasvir
• velpatasvir

Question 19

If it ends in -buvir remember B for 5B-poly*

Answer 19

NS 5B Polymerase Inhibitor

• dasabuvir
• sofosbuvir

Question 20

For treatment of HCV in naive patients without cirrhosis, the recommended regimens are:

Question 21

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–>

Answer 21

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

Question 22

which products contain sofosbuvir?

Answer 22

Epclusa
Harvoni
Vosevi
Solvaldi

Question 23

which products must be dispensed in the original container to protect from moisture?

Answer 23

Epclusa
Harvoni
Vosevi
Solvaldi

“products containing sofosbuvir”

Question 24

which products are NOT for monotherapy in treating HCV?

Answer 24

(Sovaldi) sofosbuvir, (Olysio) simeprevir, (Daklinza) daclatasvir

• is not effective as monotherapy and is not recommended.
• Should be used with another DAA with different MOA

Question 25

DAA Drug Interactions:

**ALL DAAs are CONTRAINDICATED with _______________

Answer 25

strong CYP3A4 inducers

remember P’s
(e.g. phenobarbital, phenytoin, rifampin, rifabutin, carbamazepine, oxcarbazepine and St. John’s wort)

Question 26

DAA Drug Interactions: [Harvoni, Epclusa and Vosevi]

• the sofosbuvir containing products-

Interactions include:

Answer 26

• 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

Question 27

DAA Drug Interactions:

Ethinyl estradiol-containing products are specifically CONTRAINDICATED with ___________

Answer 27

(Technivie)- ritonavir/ombitasvir/paritaprevir

(Viekira) - a packet containing:
- 2 tablets of [paritaprevir/ritonavir/ombitasvir] &
+ 1 tablet dasabuvir BID

Question 29

Mavyret

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 29

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:

Question 30

Epclusa

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 30

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:

Question 31

Harvoni

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 31

sofosbuvir + ledipasvir

Class:

Indications:

MOA:

Dosage forms:

Dosing:

Max dose:

Contraindications:

Warnings:

Side Effects:

Monitoring:

Pearls/Notes:

Drug-Drug/Food interactions:

Question 32

Vosevi

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 32

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:

Question 33

Sovaldi

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 33

sofosbuvir

Class:

Indications:

MOA:

Dosage forms:

Dosing:

Max dose:

Contraindications:

Warnings:

Side Effects:

Monitoring:

Pearls/Notes:

Drug-Drug/Food interactions:

Question 34

Viekira Pak

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 34

paritaprevir + ritonavir + ombitasvir + dasabuvir

Class:

Indications:

MOA:

Dosage forms:

Dosing:

Max dose:

Contraindications:

Warnings:

Side Effects:

Monitoring:

Pearls/Notes:

Drug-Drug/Food interactions:

Question 35

Zepatier

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 35

elbasvir + grazoprevir

Class:

Indications:

MOA:

Dosage forms:

Dosing:

Max dose:

Contraindications:

Warnings:

Side Effects:

Monitoring:

Pearls/Notes:

Drug-Drug/Food interactions:

Question 36

ribavirin (RBV)

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

RIBA

Renal Cl (when CrCl < 50 mL/min)
In combination only
Birth defects.
Anemia: hemolytic (primary toxicity)

Answer 36

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.

Question 37

PegIntron
Pegasys

“pegylated forms”

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 37

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:

Question 38

Interferon-Beta:

Is for the treatment of ___________

Answer 38

(MS) Multiple Sclerosis

Question 39

Treatment for Hepatitis B (HBV):

Answer 39

tenofovir -nof

Nephrotoxic
Osteoporosis
Fanconi syndrome

Question 40

Preferred monotherapy NRTIs in the Tx of (HBV):

Answer 40

tenofovir disoproxil fumarate (TDF) - Viread
tenofovir alafenamide (TAF) - Vemlidy
entecavir (Baraclude)

Question 41

For ALL HBV NRTIs:

Answer 41

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.*

Question 42

Viread

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 42

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.

Question 43

Vemlidy

-lidy

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 43

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

Question 44

(TAF) tenofovir alafenamide is a substrate for ___________.

So do NOT use with _______.

Answer 44

P-gp

oxcarbazepine, phenytoin, phenobarbital, rifampin and St. John’s wort

Question 45

Baraclude

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 45

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:

Question 46

Epivir HBV

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 46

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.

Question 47

Hepsera

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 47

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:

Question 48

T-TEAL “the 5 drugs approved for treatment of HBV:

Answer 48

tenofovir disoproxil fumarate (Viread)
tenofovir alafenamide (Vemlidy)
entecavir (Baraclude)
adefovir (Hepsera)
lamivudine (Epivir HBV)

Question 49

Cirrhosis:

Answer 49

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.

Question 50

There are many causes for cirrhosis, the most common in the US are ____________

Answer 50

HCV and alcohol

Question 51

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.

Answer 51

• 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).

Question 52

Cirrhosis diagnosis:

Objective Criteria:

Increased [ AST/ALT/Alk Phos/ TBili/LDH/PT/INR]

Decreased [albumin/platelets]

Answer 52

• with a liver biopsy

” however, certain lab results can suggest cirrhosis or other typer of liver damage”

-LFT: Liver function tests:

Increase

Question 53

Normal reference range for (AST) aspartate aminotransferase:

Answer 53

10-40 units/L

• in general, the higher the values the more active (acute) the liver disease or inflammation

Question 54

Normal reference range for (ALT) alanine aminotransferase:

Answer 54

10-40 units/L

• in general, the higher the values the more active (acute) the liver disease or inflammation

Question 55

Normal reference range for albumin:

Answer 55

3.5-5.5 g/dL

• protein produced by the liver

Question 56

Normal reference range for (TBili) total Bilirubin:

Answer 56

0.1-1.2 mg/dL

• used along with other liver tests to determine causes of liver damage and detect bile duct blockage.

Question 57

Normal reference range for platelets:

Answer 57

150000-450000 cells/mm^3

Question 58

Normal reference range for (PT) Prothrombin Time / (INR) International Normalized Ratio:

Answer 58

PT: 10-13 seconds (varies)

INR: < 1.2 (for those not on warfarin)

Question 59

Albumin and PT/INR are markers of _____________ AND are likely to be altered in chronic liver disease (particularly cirrhosis).

Answer 59

synthetic liver function (production ability)

Question 60

A hepatic panel also called (LFT) Liver Function Test:

comprises of (AST, ALT, TBili, and Alk Phos) is used to _______________________________________________________________

Answer 60

-assess acute and chronic liver inflammation/disease, and for baseline and routine monitoring of hepatotoxic drugs.

Question 61

Liver disease

when a patients liver enzymes begin to normalize, lab values that go unchanged would be INR and albumin.

Answer 61

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

Question 62

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.

Answer 62

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

Question 63

Child-Pugh Classification:

A score of _________ would indicate mild disease or Class A

Answer 63

a score of less than < 7

Question 64

Child-Pugh Classification:

A score of _______ would indicate moderate disease or Class B

Answer 64

a score of 7-9

Question 65

Child-Pugh Classification:

A score of ________ would indicate severe liver disease or Class C

Answer 65

a score of 10-15

Question 66

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

Answer 66

Kava
flavocoxid

Question 67

(DILI) Drug-Induced Liver Injury

Answer 67

LiverTox website
- gives information of drugs that have an association on drug induced liver disease

Question 68

Lab Tests For Liver Disease:

• Specific LFT abnormalities can help distinguish between types of liver disease.

Question 69

Lab Tests For Liver Disease:

• Specific LFT abnormalities can help distinguish between types of liver disease.

Acute Liver toxicity, including from drugs:

Answer 69

• Increased AST/ALT

Question 70

Lab Tests For Liver Disease:

• Specific LFT abnormalities can help distinguish between types of liver disease.

Chronic liver disease (e.g. cirrhosis):

Answer 70

• Increased AST/ALT, Alk Phos, TBili, LDH, PT/INR
• Decreased Albumin

Question 71

Lab Tests For Liver Disease:

• Specific LFT abnormalities can help distinguish between types of liver disease.

Alcoholic Liver Disease:

Answer 71

Increased AST greater than > ALT, (AST will be about double the ALT), increased gamma glutamyl transpeptidase (GGT)

Question 72

Lab Tests For Liver Disease:

• Specific LFT abnormalities can help distinguish between types of liver disease.

Hepatic encephalopathy:

Answer 72

increased ammonia

normal reference range for ammonia (19-60 mcg/dL)

Question 73

Lab Tests For Liver Disease:

• Specific LFT abnormalities can help distinguish between types of liver disease.

Jaundice

Answer 73

Increased TBili

normal reference range for TBili: 0.1-1.2 mg/dL

Question 74

Hepatotoxic drugs are typically discontinued when the LFTs are _______________

Answer 74

greater than > 3 times the upper limit of normal (ULN) - - (> 150 units/L of ALT or AST)

Question 76

Select Drugs with a BOXED WARNING for LIVER DAMAGE:

-

Answer 76

• acetaminophen (high doses, acute or chronic), amiodarone
• isoniazid
• ketoconazole (oral)
• methotrexate
• nefazodone
• nevirapine
• NRTIs
• Propylthiouracil
• Tipranavir
• Valproic acid

Question 77

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.

Question 79

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.

Answer 79

1- Alcohol cessation
2- Thiamine (vitamin B1)

Question 80

Wernicke’s encephalopathy and Korsakoff syndrome are different conditions that are both due to brain damage caused by a lack of _____________.

Answer 80

vitamin B1

Question 81

Treatment programs primarily use __________ for alcohol withdrawal in inpatients.

Answer 81

benzodiazepines

Question 82

Drugs used to prevent relapses include:

Answer 82

Naltrexone (Vivitrol)
acamprosate
disulfiram (Antabuse)

Question 83

Complications with Liver Disease and Cirrhosis:

Answer 83

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
-

Question 84

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?

Answer 84

octreotide or vasopressin

• medications that vasoconstrict the splanchnic (GI) circulation can stop or minimize the bleeding.

Octreotide (selective for splanchnic vessels)

Vasopressin (non-selective)

Question 85

Complications with Liver Disease and Cirrhosis:

Treatment of variceal bleeding:

Band ligation-1
or
sclerotherapy-2

Answer 85

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”

Question 86

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?

Answer 86

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)

Question 88

Complications with Liver Disease and Cirrhosis:

Hepatic Encephalopathy:

1) Symptoms include:

2) Why does it occur?

3) How do we Treat:

Answer 88

• 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.

Question 89

Complications with Liver Disease and Cirrhosis:

Ascites:

What is it?

How do we treat?

Answer 89

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

Question 90

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 __________

Answer 90

paracentesis

Question 91

Complications with Liver Disease and Cirrhosis:

(SBP) Spontaneous Bacterial Peritonitis:

What is it?

How do we treat?

Answer 91

• 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.

Question 92

Complications with Liver Disease and Cirrhosis:

Hepatorenal Syndrome (HRS):

What is it?

How do we treat?

Question 94

Sandostatin

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 94

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:

Question 95

Vasostrict

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 95

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:

Question 96

Corgard

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 96

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:

Question 97

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:

Answer 97

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:

Question 98

Enulose

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 98

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:

Question 99

Constulose

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 99

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:

Question 100

Kristalose

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 100

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:

Question 101

Generlac

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 101

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:

Question 102

Xifaxan

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 102

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:

Question 103

neomycin

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 103

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:

Question 104

Flagyl

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 104

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:

Question 105

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 (________________)

Answer 105

• to < 2 grams/day
• ## NSAIDs
• serum Na less than < 120mEq/L

Question 106

Diuretic therapy for ascites can be initiated with either:

1)
or
2)

Answer 106

Spironolactone monotherapy

or

Spironolactone + furosemide

Question 107

___________ by itself is ineffective.

Answer 107

furosemide

Question 108

Spironolactone is initiated at a dose of _______1______ and increased to a maximum dose of ______2______ per day.

Answer 108

1) 50-100mg

2) 400mg

Question 109

When used in combination, spironolactone and furosemide, if possible, a ratio of _______________ to ___________ should be used to maintain potassium balance.

Answer 109

40mg furosemide

100mg spironolactone

Question 110

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.

Answer 110

20-75mg (4-15 mL)

Question 111

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.

Answer 111

6-8 grams per liter of fluid removed.

Question 112

spironolactone

Question 113

furosemide