Hepatology Flashcards
Functionality of the liver
bile production (for digestion of foods + activation of pro drugs)
drug/food/toxin metabolism
protein synthesis (including albumin - for oncotic pressure in vascular system, and coagulation factors)
storage/adjustment of vitamins/gluconeogenesis
Liver is heavily integrated into
GI system and is important for perfusion from the heart + vasculature system
Objective markers
aspatate transaminase
alanine transaminase
alkaline phosphatase
bilirubin
albumin
international normalized ratio
thrombocytopenia
Aspartate transaminase (AST)
increases with acute liver injury
Alanine transaminase (ALT)
increases with acute livery injury
Alkaline phosphatase (alk phos)
increases with biliary tract injury from acute liver injury (i.e. gallstone)
Bilirubin
increases with biliary tract injury from acute liver injury (i.e. gallstone) or chronic liver disease
Albumin
decreases with chronic liver disease, malnutrition, CKD, or acute inflammation
International normalized ratio (INR)
increases with chronic liver disease, warfarin, or malnutrition
Thrombocytopenia
decreases with chronic liver disease, HIT, or malignancy
Objective assessment summary
term LFTs are not true markers of liver fx: liver enzymes (AST, ALT, Alk phos) usually markers of acute liver injury
elevated bilirubin can be a sign of acute and/or chronic liver issues
chronic liver disease can decrease liver production of proteins resulting in: decreased albumin, increased INR, and/or increased bilirubin
What is the estimated incidence of drug-induced liver injury (DILI)?
14-19 cases per 100,000 persons
0.02%
What are the mechanisms/classifications of the different types of DILI?
direct
indirect
idiosyncratic
Direct
agents that are intrinsically toxic to the liver
ex. acetaminophen
Indirect
caused by the action of the drug (what it does)
ex. inducing metabolite abnormalities causing non-alcoholic fatty liver disease/steatotic liver disease
Idiosyncratic
agents that have little or no intrinsic toxicity and that cause liver injury only in rare cases
ex. beta lactams, fluoroquinolones, macrolides
What medications are highest risk for causing DILI?
acetaminophen
anti-infectives: isoniazid, beta lactam antibiotics (penicillins, cephalosporins), fluoroquinolone antibiotics, macrolide antibiotics
If suspect DILI
hold offending agent
monitoring not recommended at baseline for most (except isoniazid as will be used for months)
Acetaminophen DILI
acute ingestion of high doses (>/= 8g acetaminophen) can result in toxic levels of N-acetyl-p-benzoquinone imine (NAPQI), which causes direct heptaotoxicity
s/sx: abdominal pain, jaundice, N/S/diarrhea
if not managed, can induce irreversible liver damage
assess severity through AST, ALT, and acetaminophen concentration
Goal of acetaminophen toxicity
reverse toxic metabolite through use of N-acetylcysteine (NAC) +/- activated charcoal (only if ingested <1hr prior, prevents absorption but not if taken more than 1 hr prior)
N-acetylcysteine (NAC) MOA
binds NAPQI, decreaasing hepatotoxic effects
NAC mimics or restores glutathione –> helps conjugate NAPQI to a non-toxic metabolite (cysteine and mercapturic acid) –> can be excreted (no hepatotoxicity)
NAC indication/monitoring
based on concentration of acetaminophen (>/= 4 hours after ingestion) and timing since ingestion
NAC use determined by rumack-matthew nomogram - give NAC if level is above solid line
monitor: liver enzymes - AST/ALT (q12-24h) and s/sx
PO = IV in efficacy
Acetaminophen DILI summary
assess timing of ingestion
using APAP concentration from lab and timing of ingestion, determine need for NAC using rumack-matthew nomogram
monitor liver enzymes + s/sx of acute liver injury
if intentional overdose, psychiatry evaluation appropriate
Cirrhosis
severe, chronic, irreversible fibrosis of the liver: associated with increased morbidity and mortality; annual mortality risk is 10% or more
complications are related and increase with severity (ex. hepatorenal syndrome)
Causative factors of cirrhosis
chronic alcohol use (#1 in US) - stop drinking, can prevent progression, but can’t reverse what’s been done
viral hepatitis
metabolic liver disease (ex. hemochromatosis, nonalcoholic steatohepatitis)
cholestatic liver disease (ex. primary biliary cirrhosis)
drugs: chronic use of amiodarone, methotrexate
S/sx of cirrhosis
pruritus
fatigue
weight loss
ascites
juandice (accumulation of bilirubin)
hepatomegaly or splenomegaly
encephalopathy (confusion)
Cirrhosis complications
ascites, esophageal varices, hepatic encephalopathy, spontaneous bacterial peritonitis, thrombocytopenia, hyponatremia, hepatorenal syndrome
Diagnosing cirrhosis
s/sx
markers of hepatic function (decreased albumin, increased INR)
hepatic imaging
liver biopsy (what is really used to diagnose)
Assessing severity of cirrhosis
child-pugh score
model for end-stage liver disease (MELD): predicts 3 month-mortality risk and used in transplant prioritization (higher score, higher mortality risk)
Cirrhosis summary
irreversible disease with high morbidity and mortality
multiple complications which are interconnected, but focus on the s/sx of the pt
ideally, trying to prevent cirrhosis through alcohol cessation, treatment of viral hepatitis, monitoring/cessation of hepatotoxic meds
Ascites
fluid accumulation in the peritoneal space
s/sx: abdominal distention, abdominal pain, SOB, nausea
Ascites pathophysiology
increased pressures with portal HTN drives fluid into peritoneal space
compensatory mechanisms from portal HTN results in increased fluid retention
hypoalbuminemia (decreased albumin production, less albumin in blood, decrease oncotic pressure, fluid goes outside into peritoneal space)
Ascites goals of care
minimize ascitic fluid accumulation and sx: improving QOL
reduce need for paracentesis (invasice fluid removal)
limit SEs from therapies
prevent subsequent complications from uncontrolled ascites (SBP, hepatorenal syndrome)
Ascites management
non-pharmacologic: sodium restriction (<2g/day), assess for liver transplant
first line: aldosterone antagonist (spironolactone) + loop diuretic (furosemide)
second line: paracentesis; TIPS
avoid NSAIDs in pts with cirrhosis
Diuretics for ascites
initiate at ratio of spiro 100:40 furo PO once daily
combo is superior to monotherapy, but if using one, spiro is superior to furo in cirrhosis
SE/monitoring of diuretics
aldosterone antagonists: acute kidney injury, increased potassium, gynecomastia
loop diuretics: acute kidney injury, decreased potassium
monitoring: s/sx of ascites, SCr, K+
Paracentesis
second line for chronic management (can be used acutely if tense ascites)
indicated in refractory/resistant ascites or in cases of AKI
if >5L removed via paracentesis, albumin has been shown to decrease morbidity and mortality: administer 25% albumin IV and give 6-8g albumin per liter removed - this increases the serum albumin to have retention of more fluid in vasculature than peritoneal space
Albumin calculation
take the amount of liters removed and multiple by 6 or 8g
Ascites summary
assess s/sx
for ascites, encourage non-pharm and diuretic therapy: monitor s/sx of ascites, renal fx, and potassium; paracentesis is 2nd line, unless treatment resistant (if AKI, not responsing/resistant)
Esophageal varices (EV)
portal HTN causes hepatic/splanchnic vasodilation resulting in decreased perfusion
compensatory varices or small offshoots form: dilation of EV can occur and result in variceal bleeding, which can be severe
Risk factors for variceal bleeding
varices size (larger more likely to rupture)
cirrhosis severity
red color markings noted on endoscopy
active alcohol use
Variceal bleeding prophylaxis
placebo RCTs of non-selective beta-blockers (NSBBs) or endoscopic variceal ligation (EVL) showed decreased variceal and GI bleeding, but no mortality benefit
Primary prohlyaxis for variceal bleeding
before a bleed ever occurs
NSBB or EVL recommended monotherapy (not combo)
NSBB: indicated in window of moderate disease: MOA - why non-selective beta blockers are important
beta1 antagonism: decreased HR and CO
beta2 antagonism: splanchnic vasoconstriction
NSBBs target is to decrease CO
NSBBs SEs/monitoring
nadolol, propranolol, carvedilol
SEs: drowsiness or insomnia, bradycardia, hypotension
monitoring: HR: goal 55-60 bpm, BP: SBP > 90 mmHg, s/sx of VH
EVL
endoscopic procedure which bands off varices
used as prophylaxis and treatment - primary prevention and management of acute variceal bleed
Variceal bleeding clinical presentation
esophageal varices - asymptomatic (visualized via endoscopy)
variceal bleeding: hematemesis, melena, fatigue, lightheaded/dizziness, hypotension
Treatment of variceal bleeding
immediately upon presentation: blood transfusions (to maintain Hbg > 7), octreotide (vasoconstictor), antibiotic prohylaxis (to prevent SBP)
PPIs not recommended for variceal bleeds
Surgical procedure for variceal bleeding
endoscopic variceal ligation: gold standard to control variceal bleeding
after EVL: secondary prophylaxis (indefinitely until decompensated)
Octreotide
MOA: inhibits release of vasodilatory peptides (i.e. glucagon) resulting in splanchnic vasoconstriction and decrease in blood flow
indications: acute variceal bleed (NOT otehr types of GI bleeding) - decreases mortality and transfusion in variceal bleeds
SEs: N/V, HTN, bradycardia, hypergylcemia
monitoring: s/sx, BP, HR, BG
EVL summary
gold standard for variceal bleeding cessation
goal is EVL within 12 hrs upon presentation
bands could break and/or new varices could form so not long-term solution
Primary antibiotic prophylaxis
indications: increased risk of infections with active variceal bleeding
antibiotics recommended: 3rd gen cephalosporin (ceftriaxone)
SE: diarrhea
monitoring: s/sx of infection, not renally cleared so do NOT need to monitor SCr
duration: until hemorrhage resolution (max 7 days)
decrease mortality when used
Therapies NOT recommended
vitamin K
although INR may be elevated, vit K is NOT recommended - data does not support improvement
Secondary prohylaxis for varices
EVL: every 1-4 weeks
NSBBs: continue indefinitely (until decompensated)
SE: drowsiness or insomnia, bradycardia, hypotensino
monitoring: HR: goal 55-60 bpm, BP: SBP > 90 mmHg, s/sx of bleeding
EV summary
evaluate for primary prophylaxis to prevent variceal bleeding
for variceal bleeding, acutely manage with transfusions, octreotide, antibiotic primary prophylaxis, and EVL
after a variceal bleed, initiate secondary prophylaxis with NSBBs and/or EVL
What is the proposed underlying pathophysiology of HE?
hyperammonia
What are the primary s/sx of HE?
delirium, irritable temper, asterixis (inability to keep oustretched arms + hands in place)
What are objective markers that can be used to assess for HE?
EEG pattern: dyssynchronization of fast activity, slower delta activity, increased dysrhythmicity
For acute management, what are recommended therapies? (for HE)
lactulose 25 mL twice daily as 1st line agent
rifaximin 550mg BID for recurrent HE
2nd line: large portosystemic shunts
Counseling points for a pt taking lactulose
goal of 3-5 bowel movements a day
Spontaneous bacterial peritonitis (SBP)
annual risk of SBP in pts with cirrhosis and ascites is 10-30%
due to be from bacterial translocation, in which bacteria cross the intestinal barrier
SBP clinical presentation
fever, abdominal pain/tenderness, leukocytosis (increased WBC), encephalopathy, asymptomatic
SBP diagnosis
therapeutic paracentesis: positive ascitic fluid bacterial culture; ascitic fluid with >/= 250 cells/mm^3 polymorphonuclear leukocytes
PMNs = WBC from fluid x % neutrophils
SBP treatment
antibiotics recommended: 3rd gen cephalosporin (ceftriaxone)
SE: diarrhea
monitoring: s/sx of infection (temp, WBC, cultures), not renally cleared so do NOT need to monitor SCr
duration: 5-7 days
SBP treatment
albumin has been shown to decrease mortality and AKI/HRS in pts with SBP
day 1: 1.5g/kg x1
day 3: 1g/kg x1
based on actual body weight!
SBP secondary prophylaxis
recurrence of SBP within 1 year is 70%
recommended to initiate SBP secondary prophylaxis with antibiotics and avoid PPIs (which increase risk of SBP)
sulfamethoxazole/trimethoprim (monitor: SCr, electrolytes, CBC), ciprofloxacin (monitor: mental status, CBC, renal fx)
duration: indefinite
SBP summary
evaluate need for antibiotics for treatment: longer SBP treatment duration is not better
initiate secondary SBP prophylaxis with bactrim or cipro
monitor for SEs and future SBP
Other hepatic issues
drug dosing considerations in liver insufficiency
viral hepatitis (C)
Dosing in liver insufficiency
no endogenous marker for heaptic clearance that can be used to guide drug dosing
things to consider: extent of hepatic metabolism/activation of the med - decreased metabolism and activation with cirrhosis; severity of liver disease; highly protein bound drugs –> increase free drug conc, but not total drug conc; consider avoiding/limiting hepatotoxic meds
Hepatology management overview
evaulate risk factors, subjective/objective markers of acute and/or chronic liver insufficiency
managment of acute liver injury is focused on removal/reversal of offending agent
treating cirrhosis focuses on managing individual complications as they arise
drug dosing in hepatic insufficiency is difficult
