hepatic diseases Flashcards
hepatic blood flow
inferior of superior mesenteric vein - portal vein - liver - sinusoidal spaces (space of Disse) - hepatocytes filter blood and blood moved back in the hepatic vein - inferior vena cava
normal liver function
digestive functions endocrine functions clotting functions plasma proteins organic metabolism cholesterol metabolism excretory/degradative functions
drug metabolism
phase I - non-synthetic reactions, REDOX* and hydrolysis, may detoxify a substance or make it toxic, typically involves CYP enzymes, may involve alcohol and aldehyde dehydrogenase
phase II - conjugation reactions, typically render a substance non-toxic
hematological fxns
receives around 25% of cardiac output
removes old or damaged RBCs
synthesizes plasma proteins, transport nutrients and clotting factors
AST
aspartate aminotransferase
normal values*: 0-50 IU/L
found in: liver, heart, skeletal muscle, kidney, brain, spleen, pancreas and lungs
elevated in: any disease that causes injury/damage to above tissues
ALT
alanine aminotransferase normal values*: 5-60 IU/L found in liver, heart, muscle and kidney more specific for liver injury than AST elevated in: cirrhosis, obstructive jaundice and hepatitis
Alk Phos
Alkaline Phosphatase
normal values*: 35-130 IU/L
found in: bone, liver and placenta (cells that line bile duct)
elevates in: obstructive jaundice, liver lesions, cirrhosis, paget’s disease, metastatic bone disease
GGT
gamma glutamyl transferase
normal values*: 0-85 IU/L (men have higher levels due to prostate)
found in: liver, kidney, prostate and spleen
elevated in: cirrhosis, cholelithiasis, biliary obstruction, chronic alcohol use
bilirubin
normal value: 0-1.4 mg/dL
direct/conjugated normal value: 0-0.3 mg/dL
both conjugated and unconjugated will elevate in hepatitis and cirrhosis
direct/conjugated - associated with RBC destruction
unconjugated - associated with liver blockage/destruction
LDH
lactate dehydrogenase
normal range: 90-200 IU/L
found in: liver, kidney, heart, lungs
not specific for liver dysfunction, only tissue breakdown
serum albumin
normal level: 3.6-5 g/dL
low in liver disease
coagulation
INR, PT and aPPT
elevated in cirrhosis
ammonia
NH3
normal values: 15-50 micromol/L
produced from intestinal bacteria
converted to urea in liver
BUN
blood urea nitrogen
normal values: 10-20 mg/dL
low in cirrhosis
cholesterol
may be low
LFT vs LIT
LFT = liver function test -albumin -bilirubin -cholesterol -BUN -INR LIT = liver injury test -AST -ALT -Alk Phos -GGT
hepatocellular test magnitude
AST/ALT
over 10x normal - hepatitis, drugs, ischemia
under 10x normal - broad diagnosis
components of liver disease
drugs* chronic alcohol consumption* chronic viral hepatitis* metabolic liver disease immunologic diseases vascular disease
hepatitis A
acute viral infection
typically self-limiting
transmission - fecal-oral
commonly associated with: poor sanitation and hygiene, overcrowded areas, travel
supportive care, does not lead to chronic infection
vaccination - 2 inactivated vaccines
hep A vaccines and doses
havrix:
- 1-18: 720 units, 2 doses, 0 and 6-12 mo
- 19+: 1440 units, 2 doses, 1 and 6-12 mo
vaqta:
- 1-18: 25 units, 2 doses, 0 and 6-18 mo
- 19+: 50 units, 2 doses, 0 and 6-18 mo
twinrix (also includes HBV): 18+, 720 units, 3 doses, 0, 1 and 6 mo
CDC recommendations for hep A vaccination
**all children at 1 year of age
**travelers to countries that have risk of infection
**anticipating close contact with an international adoptee from a country of high endemicity
age 2-18 in communities with high disease incidence, men who have sex with men, illegal drug users, persons with occupational risk for infection, persons who have clotting factor disorders, persons with chronic liver disease
hepatitis B
not self-limiting - will need treatment
transmission: sexually, parenterally, perinatally
complications: cirrhosis, hepatocellular carcinoma
chronic HBV: detectable serum levels or past 6 months
HBV vaccinations
engerix-B
- 0-19: 10 mcg at 0, 1 and 6 mo
- 20+: 20 mcg at 0, 1 and 6 mo
-dialysis: 40 mcg at 0, 1, 2 and 6 mo
recombivax HB
- 0-19: 5 mcg at 0, 1 and 6 mo
- 20+: 10 mcg at 0, 1 and 6 mo
-dialysis: 40 mcg at 0, 1, and 6 mo
comvax (+HIB): 6 wk-15 mo, 5 mcg at 2, 4, 12-15 mo
pediarix (+DTaP, IPV): 6 kw-6 yr, 10 mcg at 2, 4 and 6 mo
twinrix (+Hep A): 18+, 20 mcg at 0, 1 and 6 mo
HBV vacc. recommendations
**infants
**those with a h/o STDs and persons with a h/o multiple sex partners (over 1 partner/6 months)
**healthcare/public safety workers with exposure to blood in the workplace
**chronic dialysis/ESRD patients including predialysis, peritoneal dialysis and home dialysis patients
previously unvaccinated children under 19, adults at risk, adults seeking vaccination, MWHSWM, current or recent inj-drug users, household contracts/partners of persons with HBV infection, clients/staff of institutions for the developmentalyl disabled, international travelers to regions with 2+% prevalence of HBV infection, recipients of clotting factor concentrates, STD clinic patients, HIV patient/HIV testing patient, drug abuse treatment and prevention clinic patients, correctional facilities inmates, persons with chronic liver disease
Hep C
most common BBP, transmission: parenteral, sequelae: chronic hepatitis, cirrhosis, hepatocellular cancer
single largest risk factor is injection-drug use
screening for Hep C
**anyone born between 1945 and 1965
**current or past use of injection drugs
**patients who have ever been on hemodialysis
coinfection with HIV, received blood transfusions or organ transplantations before 1992, received clotting factors before 1987, patients with unexplained elevated ALT levels or evidence of liver disease, healthcare and public safety workers after a needle-stick or mucosal exposure to HCV-positive blood, children born to HCV positive mothers, sexual partners of HCV positive patients
drug induced liver disease
Many drugs are associated with adverse reactions involving the liver
Rare, potentially fatal, largely unpredictable outcome of drug treatment
No specific diagnostic tests for drug-induced liver disease - Important to know the patterns of drug-related pathology
Normal metabolic outcome = decrease the reactivity - However - many causes of drug induced liver disease are a result of bioactivation
hepatocellular injury
centrilobular necrosis, steatohepatitis, phospholipidosis, generalized hepatocellular necrosis
significant elevations in the serum aminotransferase
usually precede elevations in total bilibrubin and alkaline phosphatase
most injuries occur within 1 year of initiation
further subdivided based on histology/presentation
centrilobular necrosis
AKA direct or metabolite-related hepatotoxicity
damage spreads outward from the middle of a lobe of the liver
mild/early diagnosis - small amount of liver tissue, asymptomatic elevations in aminotransferases, minimal cirrhosis/recovery likely
severe/delayed diagnosis - large amount of tissue affected, NV, upper abdominal pain and jaundice
**EXAMPLE MEDICATION: ACETAMINOPHEN
acetaminophen
in overdose, bioactivated to N-Acetyl-p-benzoquinone imine (NAPQI)
NAPQI is very reactive, with a high affinity for sulfhydryl groups
glutathione provides source of available sulfhydrl groups within hepatocyte to detoxify NAPQI
when glutathione stores depleted, reacts directly with hepatocyte
administration of N-acetylcystine early after ingestion of the OD halts this process
nonalcoholic steatohepatitis (NASH)
accumulation of fatty acids in the hepatocyte (“supersize me”) - can see without drug induced cause in DM and poor diet
Engorgement with fatty acids, eventually disrupts hepatocyte homeostasis
Production of free fatty acids from excess circulating carbs, accelerates this process
May present with abdominal fullness or pain as only complaint
More severe cases: nausea, vomiting, steatorrhea, pruritus, and fatigue.
**EXAMPLE MEDICATIONS: TETRACYCLINE, VALPROATE
phospholipidosis
Accumulation of phospholipids instead of fatty acids
Amiodarone is associated with this reaction
Amiodarone and its major metabolite remain in the liver for several months after therapy is stopped
Usually develops in patients treated for more than 1 year
The patient can present with either elevated aminotransferases or hepatomegaly; jaundice is rare
generalized hepatocellular necrosis
Mimics the changes associated with viral hepatitis
Drugs causing this reaction generally do so via induction of the innate immune response
Subject to genetic polymorphism.
Wide variation in the sensitivity of the population to hepatic damage
**Example Medication: ISONIAZID
isoniazid
Slow acetylators* of the N-acetyltransferase2 (NAT2) genotype are at greater risk
Isoniazid is acetylated to acetylisoniazid, which, in turn, is hydrolyzed to acetylhydrazine.
Acetylhydrazine is toxic to the cellular proteins in the hepatocyte
Rapid acetylators detoxify acetylhydrazine rapidly, converting it to diacetylhydrazine
other presentation of drug induced liver injury
toxic cirrhosis
cholestatic injury
liver vascular disorders
toxic cirrhosis
Scarring effect of hepatitis leads to the development of cirrhosis
Some drugs tend to cause such a mild case of hepatitis that it may not be detected
Mild hepatitis can be easily mistaken for a more routine generalized viral infection.
If the offending drug or agent is not discontinued, this damage will continue to progress.
**Example Medications: METHOTREXATE (psoriasis and arthritis), VITAMIN A (causes fibrosis when taken for long periods in high doses, accelerated by ethanol)
cholestatic injury
Disturbances prevent the movement of bile through the canalicular system
More common in elderly and males
Some may have genetic predisposition
Accumulation of toxic bile acids and excretion products
**EXAMPLE MEDICATIONS: CHLORPROMAZINE, AMOXICILLIN-CLAVULANIC ACID, and CARBAMAZEPINE
liver vascular disorders
Peliosis hepatitis is a rare type of hepatic vascular lesion
Development of large, blood-filled lacunae (space or cavity)
Rupture can lead to severe peritoneal hemorrhage
**EXAMPLE MEDS: androgens, estrogens, tamoxifen, azathioprine.
assessment of drug-induced liver disease
patient history is best and most important technique assess: -environmental/occupational exposures -herbals -meds (Rx and OTC) -nutritional status -recreational drugs -vitamins/supplements potential drug reactions should be judges as to the: -timing of the reaction -pharmacokinetic considerations -information from the literature -inclusion of alternative nondrug causes -close clinical observation once drug is stopped
laboratory assessment of liver injury
no good clinical test available to determine exact type of liver damage - liver biopsy common specific patterns of enzyme elevation that have been identified and can be helpful necrotic: alkphos: x1 GGT: x1 AST: x3 ALT: x3 LDH: x3 cholestatic: alkphos: x3 GGT: x3 AST: x1 ALT: x1 LDH: x1 chronic: alkphos: x1 GGT: x2 AST: x2 ALT: x2 LDH: x1
alcoholic liver disease
most common cause of cirrhosis responsible for around 44% of cirrhotic deaths 3 main histological phases: -steatosis/fatty liver -acute alcoholic hepatitis -cirrhosis
pathophysiology - alcohol
alcohol dehydrogenase (ADH) converts EtOH to acetaldehyde
-acetaldehyde has direct toxic effects - damage to hepatocytes, induce fibrosis, couples to proteins
ethanol oxidation increases liver metabolic processes to reduction - increased reactive oxygen species, fatty liver, acidemia, hypertriglyceridemia
risk factors for ALD**
women, cumulative EtOH consumption, beer and spirits consumption, binge drinking, drinking between meals, drinking multiple different EtOH beverages
fatty liver disease
occurs in around 90-100% of EtOH abuse cases
occurs due to presence of triglycerides in hepatocytes
liver function typically stays normal
reversible with ETOH abstinence
acute EtOH hepatitis (AAH)
clinical syndrome of jaundice and liver failure
occurs after decades of heavy drinking
more common in men
typical age presentation 40-60 years old
AAH assessment: CAGE
do you feel you should Cut down on your alcohol consumption?
have people every Annoyed you by critisizing your drinking?
have you felt Guilty about your drinking?
have you ever had a drink first thing in the morning to steady your nerves (Eye-opener)>
clinical pres: rapid onset of jaundice, RUQ pain, encephalopathy
AAH assessment labs
AST: 2-3x higher than ALT ALT: elevated, but not much higher than 100 IU/L INR/PT: elevated total bili: elevated albumin: low
Maddrey’s score
***(4.6 x (prothrombin time-control prothrombin time)) + serum bilirubin in mg/dL score over 32: -poor prognosis -threshold for starting CSs -threshold for starting pentoxifylline
pentoxifylline
MOA: phosphodiesterase inhibitor that also modulates TNF-a
dose: 400 mg TID
showed decreased mortality in hospitalized patients with EtOH hepatitis
decreases the risk of hepato-renal syndrome
EtOH withdrawal
signs:
-initial: HA, tremors, sweating, NV, irritability, anorexia,
-worsen between 24-48 hours after EACH cessation
symptom appearance: within a few hours
symptom duration: around 48 hours
EtOH withdrawal treatment measures
fluid resuscitation thiamine 100 mg daily during withdrawal period multivitamins daily folic acid 1 mg daily for a few weeks benzodiazepines
clinical institute of withdrawal assessment (CIWA)
assessment tool used to aid in management
assess patient cognition and agitation
helps nurse decide when and how much benzodiazepine to administer to a patient
EtOH withdrawal - delirium tremens
characterized by: severe agitation, tremor, disorientation, persistent hallucinations, elevated HR, elevated breathing rate
appear 72-96 hours post EtHO cessation
typically resolve in 3-5 days
delirium tremens treatment
benzos: typically administer a long acting and PRN short acting
haldol - not typically used
clonidine - used for central acting affects for elevated BP and pulse; dose: 0.1-0.2 mg PO q8h during withdrawal period
EtOH withdrawal - seizures
present with around 24 hours of EtOH cessation
usually self limiting
usually respond to benzos
chronic treatment NOT indicated
cirrhosis
end stage of any chronic liver disease
progression similar regardless of initial insult
complications: portal hypertension, varices, ascites, hepatic encephalopathy and coagulation defects
determination of etiology: past medical/social history, physical presentation, laboratory exam
pathophys of cirrhosis
destruction of hepatocytes and increased fibroblasts
replacement of normal hepatic tissue
fibrous scar tissue:
-modify basic architecture of the liver, change in blood flow and liver function
loww of viable hepatocytes:
-altered metabolic breakdown process
-decreased protein synthesis
clinical presentation of cirrhosis
Jaundice Scleral icterus Bruising Anorexia Fatigue Bleeding Hepatomegaly Splenomegaly Spider angiomata Caput medusae Gynecomastia Decreased libido Testicular atrophy Pruritis Dupuytren’s contracture
labs in cirrhosis
Elevated: AST, ALT, Alk Phos, GGT, LDH, PT, bilirubin
decreased: albumin, total protein, platelets
cirrhosis complications
portal hypertension, varices/variceal bleeding
ascites, spontaneous bacterial peritonitis (SBP), hepatic encephalopathy, coagulopathies, hepatorenal syndrome (HRS)
treatment goals of cirrhosis
eliminate causes of cirrhosis
prevent further damage/disease progression
educate patients - alcohol cessation, Na restriction
identify and treat acute complications
prevent future complications
vicious cycle of portal hypertension
increase in NO, activation of RAAS and SNS, increase in ADH
increase in vasodilation, decrease responsiveness to vasoconstrictors, increase plasma volume
increased blood volume in splanchnic bed
increased resistance (and BP) in portal vein due to fibrosis of sinusoids and formation of scar tissue
cycle continues
varices
form when a patient has cirrhosis
portal HTN is so bad that body finds collateral outlets that bypass the liver to relieve this pressure - varices
can form in esophagus, stomach, abdominal wall and rectum
can quickly and dramatically lead to a life-threatening emergency
variceal bleeding risk factors
poor liver function large varices alcoholic etiology red wale markings 20% of patient will die from first bleed
signs and symptoms of variceal bleeding
hematemesis - vomiting of blood
melena - dark stick feces, containing partially digested blood
pallor, fatigue, decreased BP, increased HR, altered mental states, decreased Hgb and Hct, NV
treatment goals for variceal bleeding
maintain hemodynamic stability, protect airway, correct significant coagulopathies, prevent infectious complications, control acute bleed, prevent rebleed
airway protection in variceal bleeding
NG suction
prevent aspiration pneumonia - leading cause of death in active variceal bleed
swalloed blood: high protein load (preceipitate hepatic encephalopathy), nausea, hepatic encephalopathy
endoscopic variceal ligation
AKA banding
first line therapy
rubber band ligation system bands active varices, after 48-72 hours the varix will slough off
repeated q 1-2 weeks until entire variceal obliteration
octreotide
synthetic somatostatin analogue
MOA: selectively vasoconstricts of splanchnic vasculature, decreased splanchnic/portal blood flow, decreased portal pressure
dosing:
-load: 50-100 mcg IV bolus
-maintenance: 25-50 mcg/hr continuous infusion
treatment duration: continue 24-72 hours post bleeding cessation
PPIs for variceal bleeds
esomeprazole or pantoprazole
MOA: decrease stomach acid helps control active GI bleed
dosing:
-initial: 80 mg IV load
-maintenance: 8mg/hr continuous infusion for 72-96 hours; high dose oral PPI x 4 weeks post bleed
prophylactic antibiotics for variceal bleeds
treat with prophylactic antibiotics during acute bleed
purpose: prevention of spontaneous bacterial peritonitis
short course of antibiotics: 3rd generation antibiotics, fluoroquinolone
nonpharmacological treatment of variceal bleeds
standard therapy fails in 10-20% of cases
other surgical options pursued - balloon tamponade, transjugular intrahepatic portosystemic shunts (TIPS) - increased risk of hepatic encephalopathy
treatment algorithm for variceal bleeds
volume resuscitation + PPI + IV octrotide (around 5 days)
+endoscopic therapy (EVL)
+3rd generation cephalosporin (around 7 days)
recurrent bleed (within 5 days)?
no - initiate secondary prophylaxis
yes - repeat endoscopic therapy - TIPS - recurrent bleed (within 5 days)?
prevention of variceal bleeds
goal: decrease portal pressure
-reduce effects of sympathetic activation
-non selective Bblockers
B1 blockade - decreased cardiac output, decreased splachnic blood flow
B2 blockade - decreased splanchnic blood flow, decreased splanchnic vasodilation, unopposed a-1 stimulation (vasoconstriction)
non-selective B blockers
propranolol -starting: 10 mg BID or TID -titrate to HR and BP tolerance nadolol -start: 20 mg daily -dose adjustments needed with renal failure CONTINUE INDEFINITELY
nitrates for variceal bleeds
isosorbide mononitrate
controversial: may be used in combination with Bblockers, decrease rate of first hemorrhage
side effects: increased mortality if used alone, increased ascites development
may be good option in patients unable to undergo EVL
variceal bleed prevention
treatment w BBs
primary prevention - large varices (over 5 mm), small varices w increased bleeding risk - child pugh score B or C or red wale marks
secondary prevention - all patient with prior bleed
no benefit in patient without varices OR with small varices and low bleed risk
ascites
fluid accumulation in peritoneal space - 15% mortality in 1 year, 44% mortality in 5 years
progressive liver disease
-fluid leaves vascular space and accumulates in peritoneum
-decreased oncotic pressure - low serum albumin
-increased systemic volume - RAAS and sympathetic activated - Na/fluid retention
ascites pathophys
1) cirrhosis/portal hypertension
2) decreased protein synthesis, increased capillary permaebility, increased volume overload
3) hypoalbuminemia
4) fluid moved from vascular space to peritoneal space
5) ascites** (big, big belly)
s/sxs of ascites
abdomen pain fullness nausea SOB increased abdominal girth
ascites grading
1 - detected only on ultrasound - requires only salt restriction
2 - moderate abdominal distention
3 - marked ascitic fluid and abdominal distention
4 - AKA tense or refractory distention, unresponsive to diuretics
ascites diagnostic paracentesis
for new/worsening ascites
large bore needle inserted into abdomen to remove ascitic fluid
tests: cell count with differential, a total protein count, albumin and bacterial culture
gram stain is ordered but rarely helpful due to low conc of bacteria
SAAG (serum ascites albumin gradient
sensitive for etiology
comparison of serum albumin concentration to ascitic albumin concentration
** calculation: serum Alb - ascites Alb = SAAG
interpretation
1.1+ = ascites due to portal hypertension
under 1.1 = ascites due to other courses
alcohol cessation
DRAMATIC improvement in liver function
may resolve ascites in a few months - makes the ascites more responsive to medical therapy
sodium restriction
under 2 grams/day
water restriction unnecessary
usually used in combo w pharmacotherapy
diuretics
mainstay of treatment for stable patients
use a combo of diuretics - K sparing and loop
goal: around 0.5 L fluid loss/day
monitor: edema resolution and renal failure (SCr, BUN, electrolytes)
spironolactone
MOA: aldosterone antagonist acting in distal tubules; counteracts RAAS activation - decreased ascites
dose: start at 25-100 mg daily, max of 400 mg daily
SE: hyperkalemia, gynecomastia
**must maintain ratio of spironolactone 100:furosemide 40 at all times
furosemide
MOA: blocks reabsorption of Na in the loop of henle; helps maintain K levels (w spironolactone)
dose: start 20-40 mg daily, max 160 mg daily
SE: hypokalemia, hyponatremia (d/c at Na uber 120), acute renal failure (SCr over 2.0)
amiloride
used for patients experiencing significant and painful gynecomastia with spironolactone (replace)
MOA: blocks reabsorption of Na in the distal tubules, K sparing but NO aldosterone inhibition
dose: start 10 mg daily, max 40 mg dailt
SE: hyperkalemia, hypotension
therapeutic paracentesis`
treatment of choice for large volume/refractory ascites
complications: hypotension, hyponatremia, azotemia
must be accompanies by volume expanders - albumin: 8g/L of fluid removed
treatment algorithm for ascites
EtOH cessation, avoid NSAIDs, Na restriction
oral diuretics (spironolactone/furosemide) - titrate every 3-5 days - max: 400/160
therapeutic paracentesis with albumin infusion
transjugular intrahepatic portosystemic shunt (TIPS)
liver tranplant
spontaneous bacterial peritonitis (SBP)
“spontaneous” infection of perioneal fluid
key mechanism: bacterial translocation
assessment: patient presents w sxs, diagnostic “tap”
predisposing factors: prior SBP, low ascitis fluid total protein, high serum bilirubin
assessment of SBP
symptoms of infection: fever, chills, abdominal pain, changes in mental status
ascitic fluid analysis: polmorphonuclear leukocyte count (PMN) greater than or equal to 250 cells/mm^3***, decreased total protein, elevated neutrophil count, positive bacterial culture
PMN = WBC x % neutrophil
bacterial etiology in SBP
initiate empiric antibiotic therapy with broad-spectrum anti-infective agent - either PMN over 250 or PMN under 250 + s/sxs of infection
most common bacteria:
-gram negative aerobes: Ecoli, klebsiella pneumoniae
gram positive: streptococcus pneumoniae
treatment of SBP
ceftriaxone 2 gm IV q24h cefotaxime 2 gm IV q8h piperacillin/tazobactrum 3.375 gm IV q6h ticarcillin/clavulanate 3.1 gm IV q6h levofloxacin ciprofloxacin **treat at least 5 days
adjuctive albumin for SBP
increases likelihood of renal failure consider 1-1.5 g albumin/kg any of the following during SBP: -SCr over 1 -BUN over 30 -bilirubin over 4
antibiotics to prevent SBP
secondary prevention: treat for life
primary prevention: low ascitic protein AND one of the following:
SCr over 1.2
BUN over 25
Na under 130
child-pugh over 9 + bilibruibin over 3
drug options: ciprofloxacin 500-750 mg PO QD, TMP/SMX 1 DS tab PO QD, norfloxacin: 400 mg PO BID
pathophys of hepatic encephalopathy (HE)
substances bypass liver - remain in circulation
increased blood ammonia - decreased conversion of NH3 to urea, generated by gut bacteria and is a byproduct of protein catabolism, neurotoxic substance
s/sxs of hepatic encephalopathy
Mood disturbances Reversal of sleep/wake cycle Impaired memory Short attention span Asterixis** Slow monotonous speech Loss of fine motor skills EPS-type movement disorders Hyperventilation Seizures Confusion Coma
precipitating events of hepatic encephalopathy
increased nitrogen load - GI bleed, excessive protein, constipation, azotemia
drugs: narcotics, benzos, sedatives, diuretics
electrolyte imbalances - hyponatremia, hypokalemia
misc: infection, TIPS
diagnosis of hepatic encephalopathy
serum ammonia levels
-normal: under 35 mmol/L
-elevation does not correlate to degree of confusion
-NOT diagnostic
state of confusion or altered mental status + cirrhosis
-diagnosis largely based on clinical suspicion
treatment goals for hepatic encephalopathy
correct precipitating factors reverse overt encephalopathy reduce nitrogen load in gut avoid recurrence assess need for long term therapy
treatment approaches for hepatic encephalopathy
reducing ammonia blood concentrations
-dietary restrictions
-drug therapy to inhibit production or increase removal
inhibition of GABA-benzodiazepine receptors
avoid precipitating factors
nutritional management
protein restriction was done in past - small meals or liquid nutritional supplements evenly distributed throughout the day
milk or vegetable sources of protein preferred - increased calorie or nitrogen ratio, increased fiber
branched chain AAs
lactulose for HE
MOA: hydrolyzed in colon, osmotically active, lowers colonic pH and binds NH3
dose:
- initiation: 45 ml/hr until catharsis
- maintenance: 15-45 ml/hr q8-12h; titrate to 3-4 soft bowel movements daily; maintain regimen to prevent HE
monitoring: electrolytes, stool frequency/consistency
metronidazole for HE
MOA: decreased gut flora = decreased production of NH3
dose: 250 mg PO q6-12h
SE: peripheral neuropathy, disulfram-like reaction, metallic taste
neomycin for HE
Oral aminoglycoside
Dose: 3-6 g/daily (divided doses), Max duration = 2 weeks
Side Effects: Irreversible ototoxicity, Reversible nephrotoxicity
**No longer considered 1st line antibiotic
rifaximin for HE
Approved in 2005 for HE
Dose: 400 mg q8h x 5-10 days duration (treatment); 550 mg BID (prevention)
SE: headache, flatulence
Costly
false NTs for HE
Flumazenil
- No long-term benefit
- Parenteral
- Dose: 0.2 mg up to 15 mg/day
- Not for long term treatment
coagulation defects
Liver synthesizes most proteins responsible for hemostasis
Liver damage can cause the following:
-Reduction in synthesis of clotting factors
-Excessive clot breakdown
-Disseminated intravascular coagulation
-Thrombocytopenia
-Platelet dysfunction
thrombocytopenia
Occurs in up to 70% of patients
Pathophysiology:
-decreased platelet production (decreased thrombopoetin)
-Splenic sequestration (splenomegaly due to portal HTN)
-Increased PLT destruction
Treatment: Platelet transfusion
Vit K for coagulation defects
MOA: Essential factor in production of coagulation proteins
Evaluation:
-increased INR, PT and PTT
-Abnormal bruising, bleeding & skin stigmata
Treatment:
-10 mg vitamin K subcutaneously x 3 days
-Consider FFP to rapidly replete plasma proteins
-DDAVP sometimes used as adjunct
hepatorenal syndrome
Development of renal failure in the presence of liver failure - Without alternate explanation
around 8-20% of cirrhotic patients will develop
Mortality:
Type 1 (rapid): median survival = 14 days
Type 2 (slow): median survival = 6 months
pathophysiology of hepatorenal syndrome
Increased renal vasoconstriction which leads to decreased renal function
Vasoconstriction due to:
-Renal response to increased cardiac output
-Low arterial pressure
-Increased RAAS and sympathetic nervous system activation
-Increased vasodilatation in splanchnic bed
Eventually – damage to heart (hepatic cardiomyopathy) - Further reduction in renal blood flow
hepatorenal syndrome risk factors
low urinary Na excretion low serum Na low mean arterial pressure high RAAS activity high serum K previous episodes of ascites absence of hepatomegaly esophageal varices poor nutrition SCr above 1.5 mg /dL
treatment of hepatorenal syndrome
d/c diuretics and treat cause (if known) 1st line: -albumin + octreotide + midodrine -albumin dose: 1g/kg on 1st day then 20-40 g/day -octreotide dose: 100 mcg SQ TID or cont infusion midodrine dose: 5-7.5 mg PO TID 2nd line: liver transplant only definitive cure - prolongs survival
using common meds in liver impairment
Consider the Following:
-Will the drug will adversely affect the liver ? (uncommon)
-Will the drug’s metabolism will be impaired? (common)
-Will the drug might contribute to a liver disease complication? (common)
General Guidelines:
-Start with a low dose and/or reduced dosing frequency, and titrate slowly.
-Patients with chronic liver impairment may also have renal impairment
pain management in liver disease
Cirrhotics may develop pain for a variety of reasons
Choice of appropriate agent tricky
More prone to adverse effects of medications for pain
Balance risk/benefits on individual basis
visceral or musculoskeletal: acetaminophen under 2-3 g/day - tramadol 25 mg q8h - hydromorphone 1 mg q4h, fentayl 12.5 mcg q72h, DC tramadol!!
neuropathic pain - nortripyline 10 mg QHS OR desipramine 10 mg QHS + gabapentin 200 mg QD OR pregabalin 150 mg BID + acetaminophen under 2-3 g/day
acetaminophen general considerations
Misperceived as dangerous in cirrhotics
T1/2: 2x healthy controls
Studies in cirrhotics
-Not a lot of data, no evidence-based guidelines
Group of 10 hepatologists published:
-Long term APAP use allowable in cirrhotics at reduced dose of 2-3 g/day
NSAID general considerations
in general-AVOID**
Increased serum levels: Metabolism through CYP, Highly protein bound
Renal impairment: Increase Na/H20 retention, Counteracts diuretics, Precipitate HRS
Gastric bleeding: Varices, thrombocytopenia
opioids in liver disease
common precipitants of HE/hospitalizations
metabolized in liver (fentanyl and hydromorphone = no active metabolites)
recommend: avoid if possible, use tramadol first, use fentanyl or hydromorphone 2nd line
child-pugh disease staging
bilirubin (mg/dL): - 1-2 = 1 point - 2-3 = 2 points - over 3 = 3 points albumin (mg/dL): - over 3.5 = 1 point - 2.8-3.5 = 2 points - under 2.8 = 3 points ascites: - none = 1 points - mild = 2 points - moderate = 3 points encephalopathy (grade): - none = 1 point - 1 and 2 = 2 points - 3 and 4 = 3 points prothrombin time (sec): - 1-4 = 1 point - 4-6 = 2 points - over 6 = 3 points STAGE 5-6 point = A 7-9 points = B 10-15 points = C
child-pugh survival rates
A: 1 year = 100%; 2 year = 85%
B: 1 year = 81%; 2 year = 57%
C: 1 year = 45%; 2 year = 35%
MELD score`
mayo end-stage liver disease scoring
calculated score: based on SCr, bilirubin, INR and etiology of liver diease
score from 6-40 and used to classify disease severity
used to assess liver transplant
under 15 = survival better with current liver
liver transplant contraindications
Compliance issues HIV infection Lack of social support Uncontrolled infection Severe extrahepatic disease Body Mass Index over 35 kg/m2 Age over 70 years
