Block 1: Drug induced Liver Injury/Cirrhosis

Question 1

What is the liver function?

Answer 1

1. Bile production
2. Fat-soluble vitamin storage and metabolism (ADEK)
3. Drug metabolism
4. Billirubin metabolism
5. Produces proteins for blood clotting and osmotic pressure
6. Metabolizes nutrients from food to produce energy prn

Question 2

Most common DILI medications?

Answer 2

1. Alcohol
2. Antibiotics
3. Antiseizure
4. APA

Most common cause of drug withdrawal, difficult to detect

Question 3

Fisk facotors of DILI?

Answer 3

1. Older age
2. Females with severe hepatotoxicity
3. Males with azathioprine, anabolic steroids, amox-clav
4. Genetic polymorphisms
5. DDI
6. Livertox score

Question 4

How do you diagnose DILI?

Answer 4

Patient with one of the following:
1. AST or ALT >5x ULN or ALP >2x (or fromt baseline) on 2 separate occasions
2. Total serum bilirubin >2.5 mg/dL with elevated AST, ALT or ALP
3. INR >1.5 with elevated AST, ALT, ALP

Question 5

What are the elemetns that a drug might cause liver injury?

Answer 5

1. Drug exposure preceded injury
2. Causes of liver disease are excluded
3. Drug discontinuation leads to improvement in the liver injury
4. Rapid and severe recurrence occurs if there is repeated exposure to the drug (rechallenge)

Question 6

Types of hepatotoxic medications classes?

Answer 6

1. Antibiotics/Antimicrobial
2. Immunosuppressive
3. Birth control
4. NSAIDs
5. Antineoplastic
6. Antiepiletic

Question 7

MOA of APA toxicity?

Answer 7

Question 8

What is the tx of APAP toxicity?

Answer 8

1. NAC: most effective within 8hr of ingestion

Question 9

N-acetylcysteine?

MOA, Forms, Monitoring

Answer 9

MOA: repletes glutathione reserves by providing cysteine, an essential precursor to glutathione production (binds to toxic metabolites and scavenges free radicals)
Forms: IV or Oral (rotten eggs)

Tx continues untils APAP levels are undetectable, PT/INR near normal, Encepalopathy resolved, transaminase levels trending down

Question 10

What are liver chemistries?

Answer 10

Markers of injury not function

Question 11

What is on a liver comprehensive metabolic panel?

Answer 11

1. ALT
2. AST
3. ALP
4. Bilirubin
5. Albumin

Question 12

What is cirrhosis?

Answer 12

1. Caused by chronic liver injury
2. Regenerative nodules surrounding dense fibrotic material
3. Impacts portal BF, hepatocyte perfusion, hepatic synthetic functions
4. Leads to portal HTN. varices, variceal bleeding, ascites, infection, encephalopathy, and hepatocellular carcinoma

Question 13

What is varices?

Answer 13

Enlarged esophagus and stomach veins

Question 14

Common causes of cirrhosis?

Answer 14

1. Alcoholism
2. Chronic Hep C
3. NAFLD

Question 15

Sx of cirrhosis?

Answer 15

1. Asymptomatic
2. SPLENOMEGALY
3. Jaundice
4. Gynecomastia
5. Ascites, edema
6. Malaise, anorexia, weight loss
7. Encephalopathy

Question 16

What are the labs of cirrhosis?

Answer 16

1. Hypoalbuminemia
2. PT elevation
3. Thrombocytopenia
4. Elevated ALP, AST, ALT, GGT

Question 17

How do you diagnose to severity of liver disease?

Answer 17

Child-Pugh Classification

Question 18

A patient has the following information: albumin 4.1 g/dL (41 g/L), serum bilirubin 3.3 mg/dL (56.4 µmol/L), prothrombin time that is 5 seconds prolonged, no ascites, and no encephalopathy. In terms of Child-Pugh score, what is the patient’s severity?

Answer 18

Grade B

Question 19

What is the geneal approaches of cirrhosis tx?

Answer 19

1. Identify and eliminate causes
2. Assess risk for variceal bleeding
3. Evaluate for signs of ascites
4. Monitor for HE (lower ammonia)
5. Monitor for signs of hepatorenal syndrome, pulmonary insufficiency, and endocrine dysfunction

Question 20

What is protal HTN from mechanism to diagnosis?

Answer 20

1. Resistance to portal blood flow = increased resistance and structural changes
2. Asymptomatic utill complicatins (ascites, variceal, SBP)

Diagnosis: Known RF and clinical manifestations, if doubt, HVPG

Question 21

What are the strageties to treat variceal bleeding?

Answer 21

1. Primary prophylaxis (prevention of first episode)
2. Tx of acute variceal hemorrhage
3. Secondary prophylaxis (prevention of rebleeding)

Question 22

Tx of primary variceal bleeding prophylaxis?

MOA, Dosing, CI

Answer 22

Nonselective B-blocker: Propranolol, nadalol, carvedilol

MOA: Reduce portal pressure by decreasing cardiac output by blocking beta-1 receptors and decrease in splanchnic blood by blocking beta-2 receptors

Dosing: propranolol 20-40 mg PO BID or nadalol 20-40 mg daily
(Titrate dose to resting HR of 55-60 beats/min, SBP > 90 mmHg)

CI: Given with present varices not to prevent the formation of

Question 23

Tx of acute variceal hemorrhage?

Answer 23

Medical emergency
1. Adequate fluid resuscitation
2. Protection of airway for aspirating blood
3. prophylaxis against SBP/other infections
4. control bleeding, prevention re-bleeding
5. prevent AK, preserve liver function
6. Abx to prevent SBP: IV ceftriaxone 1g/day
7. 6. Stop/slow bleeding:
* Octreotide IV bolus 50 mcg followed by continuous IV infusion of 50 mcg/hr (up to 2-5 days)

ADR: bradycardia, HTN, arrhythmia, abdominal pain

Question 24

Tx of secondary variceal bleeding?

Answer 24

1. TIPS procedure 2. Nadolol or propranolol only w/ EVL (endoscopic variceal ligation)

Question 25

Which of the following represents an appropriate goal for a patient started on propranolol for variceal bleeding prophylaxis?

Answer 25

Heart rate of 55 to 60 beats/min; systolic blood pressure > 90 mm Hg

Question 26

Describe the patho of ascites?

Answer 26

Question 27

What is ascites?

Answer 27

Accumulation of an excessive amount of fluid within the abdomen Major complication of cirrhosis

Question 28

Tx of ascites?

Answer 28

1. Paracentesis for new-onset 2. Sodium restriction of 2000 mg/day 3. Aldosterone antagonist or aldosterone antagonist + loop diuretic **(Spironolactone 100 mg PO QD + furosemide 40 mg PO QD)** 5. Abstain from alcohol

Question 29

What is Spontaneous Bacterial Peritonitis?

Answer 29

Infection of ascitic fluid from altered intestinal permeability and resultant bacterial translocation

Question 30

Spontaneous Bacterial Peritonitis | Causes, sx, diagnosis

Answer 30

**Causes:** E. coli, Kleb pneumonia, pneumococci **Sx:** Abdominal pain, diarrhea, vomiting **Diagnosis:** (+) ascitic fluid bacterial culture and elevated ascitic fluid cell count of leukocytes

Question 31

Tx of Spontaneous Bacterial Peritonitis?

Answer 31

Broad spectrum Abx: 3rd gen cephalosporin (cefataxime-Claforan or - ceftriaxome-Rocephin) MDRO: piperacillin/tazobactam (zosyn) Add vancomycin if MRSA

Question 32

Which of the following symptoms is most consistent with Spontaneous Bacterial Peritonitis?

Answer 32

Increased leukocytes in ascites fluid

Question 33

What is hepatic encephalopathy?

Answer 33

Functional disturbance of the brain caused by liver insufficiency: 1. Neurotoxic accumulation 2. Ammonia is most common, but also glutamine, benzodiazepine receptor agonists, and aromatic amino acids 3. Increased levels of ammonia in acute and chronic liver disease

Question 34

Sx of hepatic encephalopathy?

Answer 34

1. Confusion 2. Personality changes 3. Disorientation 4. Depressed level of consciousness 5. Lethargy Can cause coma and death

Question 35

Non pharm of hepatic encephalopathy tx?

Answer 35

1. Protein Restriction: 1 to 1.5g/kg/day 2. High fiber diet (favor plant-based proteins- beans, etc)

Question 36

Pharm of hepatic encephalopathy?

Answer 36

1. Non-absorbable disaccharide -Lactulose: Dose 15-45mL PO Q8-12 hours targeting 2-3 soft stools/day, Rectal enema, and can consider PEG 3350 2. Abx: Neomycin, Metronidazole (don't use) - high risk for neurotox and lower effectiveness 3. Rifaximin ($$$) - Low systemic absorption

Question 37

Your patient has a history of chronic alcohol use and cirrhosis and now presents with altered mental status with alternating delirium and loss of consciousness. He has no evidence of ascites or hematemesis. Which of the following is your immediate next step?

Answer 37

Assessing ammonia levels and screening for hepatic encephalopathy.

Question 38

ADME changes of heptaic encephalopathy treatment?

Answer 38

1. Increased sensitivity of NSAIDs, benzos, opiates 2. Reduced liver blood flow, loss of CYP enzyme activity, decreased first pass extraction, hypoalbuminemia, ascites, impaired biliary excretion, etc 3. Requires closer monitoring