DILD and Cirrhosis- Dr. Ochs

A liver function test or LFTs includes…

• AST

• ALT

• Alkaline phosphatase (Alk phos, ALP)

• bilirubin

• albumin

What is a normal INR ratio?

0.9-1.1

What are the 2 types of liver disease?

1. hepatitis

2. cirrhosis

What does a MELD Score stand for? What does it assess?

• stands for Model for End-Stage Liver Disease

• assess likelihood of survival in pts. w/ liver disease and prioritizes pts. for liver transplants

What does a Child-Pugh Score assess? (will not have to calculate on exam)

assess liver function and estimates liver’s ability to metabolize drugs in pts. with decompensated liver disease

How does hepatitis or cirrhosis effect drug metabolism?

hepatitis—> unchanged/slightly decrease

cirrhosis—> significant decrease

What are some risk factors for DILD?

• alcohol consumption

• age >60

• type 2 DM

• Rheumatoid arthritis

Liver damage can either be acute hepatocellular or cholestatic. What lab findings would you find for each?

acute hepatocellular- HIGH AST and ALT

cholestatic (gallbladder)- HIGH ALK PHOS

R factor can be calculated to differentiate the type of liver damage present. A R>5, R≤2, and R between 2-5 mean…

• R>5 hepatocellular injury

• R≤2 cholestatic injury

• R 2-5 mixed injury

What drugs cause hepatocellular injury?

• acarbose

• allopurinol

• fluoxetine

• losartan

What drugs can cause centrilobular necrosis?

ACETAMINOPHEN

What drugs can cause Nonalcoholic Steatohepatitis (NASH) or Nonalcoholic fatty liver disease (NAFLD)?

• tetracycline

• valproate

What drugs can cause alcoholic steatohepatitis?

alcohol

What drugs can cause phospholipidosis?

amiodarone

What drugs can cause generalized hepatocellular necrosis?

• isoniazid

• ketoconazole

What drugs can cause toxic cirrhosis?

• methotrexate

• vitamin A

Cholestatic injury is defined by…

Alk Phos x3 ULN

What drugs can cause cholestatic injury?

• erythromycin

• amoxicillin-clavulanic acid

• carbamazepine

• IV vitamin E

• Total parental nutrition (TPN)

What drugs can cause mixed hepatocellular and cholestatic injury?

• phenytoin

• sulfonamides

What is the antidote to APAP toxicity? What is the dose based on?

antidote- N-acetylcysteine

dosed based on Rumack-Mathew Nomogram

What method is used to determine the likelihood of a certain drug causing drug-induced liver injury?

RUCAM

(FYI: this is different from child-pugh because child-pugh focuses on the liver’s ability to metabolize and rucam focuses on the likelihood a drug will cause injury)

PRACTICE:

Significantly elevated Alk Phos is most closely related to which kind of liver damage/injury?

cholestatic

PRACTICE:

What is the MELD score tool used for?

prioritizes liver transplant

PRACTICE

If left undetected, what can NAFLD progress to?

NASH

PRACTICE:

What drugs are associated with steatohepatitis?

• tetracycline

• valproate

• alcohol

PRACTICE:

What drugs are associated with toxic cirrhosis?

• methotrexate

• Vit A

What are some common causes of cirrhosis?

• alcoholism

• chronic hepatitis C

• Non-alcoholic fatty liver disease (NAFLD)

• others: autoimmune hepatitis, primary biliary cirrhosis, medications

What are signs of decompensated cirrhosis?

• variceal bleeding

• ascites

• encephalopathy

What are some complications of liver fibrosis?

FYI on the general approach to variceal tx

When is primary prophylaxis to prevent variceal hemorrhage indicated?

• pts. with SMALL varices AND presence of risk factors

• any pt. with medium/large varices

What are the 2 general tx options for prophylaxis of variceal hemmorhage?

• Endoscopic variceal ligation (EVL)

• non-selective beta-blocker (NSBB)

What is Endoscopic variceal ligation? When is it used 1st line for primary prophylaxis?

• “banding of varices”

• (basically we put a band around the varices, that cuts off the blood flow and then it falls off and dies!)

• 1st line IF patient cannot tolerate or are contraindicated to NSBBs

  • not really used for small varices, more for medium/large

What NSBB are used for primary prophylaxis of varices?

• propanol

• nadalol

• carvedilol (has some a-activity)

NSBB should be titrated to goal HR of ____-____ BPM or max tolerated dose.

55-60 BPM

SUMMARY ON PROPHYLAXIS MANAGEMENT OF VARICES:

What prophylaxis tx can be used for the following:

1. no varices, low risk small varices

2. small varices with risk factors for bleeding

3. Medium or large varices

1. primary prophylaxis NOT recommended

2. NSBB preferred

3. NSBB and EVL

An acute variceal hemorrhage is a medical emergency. What are the non-pharm and pharm options for management?

non-pharm (procedures): EVL, sclerotherapy, balloon tamponade, TIPs

PHARM:

• Octreotide and antibiotic

• vasopressin+nitroglycerin AND antibiotic

Of the pharm tx for acute variceal hemorrhage, which is 1st line, which is 2nd line?

1st- Octreotide

2nd- vasopressin+nitroglycerin

What is the max duration for vasopressin use?

24 hours (in order to reduce ADRs)

Why must nitroglycerin be given with vasopressin?

to decrease risk of ischemia

Why is an antibiotic taken with octreotide or vasopressin+nitroglycerin in acute variceal hemorrhage?

to prevent SBP

What antibiotic is preferred in acute variceal bleeding to prevent SBP?

ceftriaxone

After an acute variceal bleed, what must be initiated?

secondary prophylaxis

In what 2 scenarios is secondary prophylaxis of variceal hemorrhage not needed?

if the pt. had SHUNT surgery or TIPS

What is used for secondary prophylaxis of variceal hemorrhage?

• Traditional NSBB—> BUT ONLY NADOLOL OR PROPRANOLOL

  • NOT CARVEDILOL!!!!!!!!!!!!!!!!!!!!!

• EVL

How does ascites present?

• abdominal bulging

• shifting flank dullness

• positive fluid wave

What lab value would indicate the ascites is due to portal hypertension?

SAAG ≥1.1 g/dL

What should be performed on all new-onsets of ascites?

abdominal paracentesis to rule out infection

What are the pharm tx options for ascites? What pharm should be d/c?

• tx: diuretics

• d/c: anything that may cause Na+/water retention

What electrolyte is important to monitor with the use of diuretics?

potassium (K+)

What is the PREFERRED diuretic regimen for ascites? If a combination of diuretics is not possible, which is preferred?

spironolactone + furosemide (if solo—> spironolactone preferred)

What is the dosing regimen for diuretics in ascites? What is the ratio?

Dosing: ratio of spironolactone 100mg PO daily and furosemide 40mg PO daily

(100:40 mg)

If a paracentesis is performed, what may you consider giving the patient to prevent the fluid from immediately accumulating again?

IV albumin (only given if over >5L removed)

What is SBP? What is it caused by?

• SBP is spontaneous bacterial peritonitis and is a bacterial infection OF THE ASCITIC FLUID

• caused by bacteria like E. coli, pneumonia, and others

Symptoms of SBP? (not that imp)

fever, abdominal pain and tenderness, confusion (from encephalopathy)

What signs are DIAGNOSTIC of SBP?

• positive culture OR

• PMNs ≥250 cells/mm³ in ascitic fluid

Long-term SBP prophylaxis is for anyone that is…

high risk

Short-term SBP prophylaxis is for…

acute variceal bleeds

What are the tx options for long-term prophylaxis?

• ciprofloxacin

• sulfamethoxazole/trimethoprim

For TREATMENT (not prophylaxis) of SBP what are the 1st line options? Include the drug, dose, dosage form, and frequency

• Cefotaxime 2g IV q8h

• Ceftriaxone 2g IV q24h

When is piperacillin-tazobactam+ vancomycin used for tx of SBP?

• 2nd line (risk of drug-resistance or nosocomial infection)

What is the duration of 3rd gen cephalosporins for tx of SBP?

5-7 days

What are the criteria for albumin to be given with SBP tx?

should be given when the ascitic fluid PMN ≥250 cells/mm3 AND one of the following:

• SCr >1mg/dL

• BUN >30 mg/dL

• Total bilirubin >4 mg/dL

When is secondary SBP prophylaxis indicated? What is the duration of tx?

• indicated for ANY patient that survives an episode of SBP

• duration: life-long

What are the secondary SBP prophylaxis tx options?

• CIPROFLOXACIN

• SULFAMETHOXAZOLE/TRIMETHOPRIM

What causes hepatic encephalopathy?

AMMONIA accumulation

What are some symptoms of hepatic encephalopathy?

• altered behavior

• confusion

• loss of consciousness

• disoriented

What is the name of the criteria that grades hepatic encephalopathy?

West Haven Criteria

What are some non-pharm ways to correct hepatic encephalopathy?

reduce protein intake (choose veggie/dairy protein> meat)

What are the pharm options for hepatic encephalopathy? say which is 1st line.

• Lactulose- 1st LINE

• antibiotics

• zinc

What is the MECHANISM of lactulose?

• enhances diffusion of ammonia from blood to gut

• ACIDICFICATION results in conversion of ammonia into ammonium

• ammonium is then excreted

What is dose is lactulose available as? What is the dosing for episodic or persistent hepatic encephalopathy?

• available as 10g/15 ml solution

• episodic: initiate 16.7 PO q1-2h until BM

  • reduce to 10-30g PO q8-12h, and titrate to 2-3 soft BM

• persistent: titrate to 2-3 soft BM

What is used in combination with lactulose as a SECOND LINE AGENT for hepatic encephalopathy? (Include drug, dose, route, and frequency)

Rifaximin 550mg PO BID

Rifaximin is preferred over _____________ or ________________ in hepatic encephalopathy.

neomycin or metronidazole

what is the mechanism for rifaximin and zinc?

rifaximin- reduces gut bacteria

zinc- aids in conversion of ammonia to urea