ACUTE LIVER FAILURE

Definition :
1. Synthetic liver failure (INR > 1.5) with hepatic encephalopathy (HE)
2. No underlying cirrhosis
3. HE begins within roughly <26 weeks from onset of jaundice
Classification :
1. Hyperacute acute liver failure : interval between onset of symptoms (usu jaundice) and
encephalopathy <1 weeks
- Carries a higher risk of immediate deterioration due to cerebral edema
- Common causes viral hepatitis and acetaminophen
- If the patient survives immediate illness, greater likelihood of liver recovery and thus
avoiding transplantation
2. Subacute acute liver failure : interval >4-6 weeks between onset of jaundice and
encephalopathy
- Less likely to cause cerebral edema and immediate death
- Clinically this may appear a bit more like cirrhosis (a gradual process with ascites)
- There is a lower likelihood of liver recovery,
- more likely to require transplantation
Etiology (most common) :
- Acetaminophen
- Viral hepatitis
- Drugs or toxin
- Ischemic hepatitis
- Autoimmune hepatitis
Etiology (less common) :
- Pregnancy related (AFLP, HELLP)
- Malignant infiltration of the liver
- Budd-Chiari syndrome (thrombosis)
- Wilson disease
- Hemophagocytic lymphohystiocytosis
Common precipitants of acute liver failure :
1. Bacterial infection (most common) : SBP, UTI, pneumonia
2. Reactivation of viral hepatitis
3. Hepatotoxic drugs including alcohol
4. Hypovolemia and electrolyte imbalance (esp sodium and potassium) :
a) gastrointestinal bleeding
b) dehydration (diarrhea, overdiuresis)
c) large volume paracentesis without albumin infusion
1. Acute kidney injury
2. Constipation
Less common precipitants of acute liver failure :
1. Iatrogenic : procedure related e.g. surgery, TIPS
2. Portal or hepatic vein thrombosis
Laboratory indications of hepatic failure :
1. Labs suggesting active or impending hepatic failure may include:
a. INR >1.5
b. Marked hyperbilirubinemia.
c. Severe elevation of transaminases.
2. Frank metabolic failure of the liver may eventually cause:
a. Lactic acidosis
b. Hypoglycemia.
c. Hyperammonemia.

Specific Treatment :
1. Review and discontinue all hepatotoxic medications
2. Steroid therapy is occasionally indicated for autoimmune hepatitis (1
mg/kg/IBW/day), alcoholic hepatitis, and some drug-induced hepatitis
3. Antiviral therapy for HBV, HCV, herpes simplex virus, varicella zoster virus,
4. N-acetylcystein IV improves transplant free-survival even in non-acetaminophen liver
failure. Dose
Supportive Treatment :
1. ALF tends to cause vasodilatory shock state (often difficult to separate from septic
shock, obtain culture if sepsis is suspected)
2. Intubation may be required for worsening encephalopathy for :
a) Airway protection from aspiration
b) Avoid hypercapnia, which can worsen ICP elevation. Target low-normal
PaCO2
3. Stress ulcer prophylaxis should be considered, even in non-intubated pts
4. Nutritional support : standard protein target 1,2-2g/kg IBW/day may be use if
ammonia level monitoring is available. Suspend feeding if marked hyperammonia
occur (>150 mM), risk of herniation.
5. Renal :
a) Treat electrolyte abnormality esp hypokalemia (increase renal ammoniagenesis)
and sodium imbalance
b) Avoid nephrotoxin
6. Infection : Low threshold for initiating empiric antibiotic therapy and culture
7. Coagulation :
a) Consider vitamin K 10 mg for 3 days (although its efficacy is minimal; rarely pts
with acute liver failure is vit-K deficient)
b) FFP transfusion is generally not indicated. High INR in liver failure does not
always correlate with tendency to bleeding (consider TEG to assess
thrombotic/bleeding tendency more accurately).
8. Endocrine : avoid hypoglycemia esp in NPO patient. D10 infusion may be required.
9. Neurology : the greatest life-threat for acute liver failure is acute HE, which often
associated with increased intracranial pressure and herniation. This is far more
dangerous than HE in cirrhosis (which isn’t associated with cerebral edema and
herniation)

HEPATIC ENCEPHALOPATHY
Types : type A (caused by acute liver failure, highly morbid condition), type B (caused by
TIPS; rare), type C (due to cirrhosis)
Grade :
I : altered behavior with normal level of consciousness, reduced attention span.
II : altered behavior with disorientation, drowsiness
III : confused, incoherent, mostly sleeping but arousable to painful stimuli.
IV : comatose and unresponsive to pain
Manifestations :
1. Main finding is a non-focal metabolic delirium with symptoms ranging from subtle
alterations of consciousness to frank coma
2. Usually more of a hypoactive form of delirium than hyperactive delirium
3. Asterixis (inability to maintain a stable posture, flapping tremmor when instructed hold
hands outstretched) is the hallmark of HE, but may be seen in other metabolic
encephalopathy (including uremia, hypercapnia, hypoglycemia). Asterixis is lost in the
most severe stages of HE.
4. Hyperreflexia, hypertonia, and clonus may also occur
5. Respiratory alkalosis is common in cirrhosis due to increased respiratory drive (may be a
useful clue to HE for a patient intubated due to hypoactive delirium)
6. Prior HE history
7. Seizures can occur, although not common.

Evaluation :
1. Immediate fingerstick glucose
2. Basic labs (liver function tests, renal function test, electrolytes including Ca/Mg/P)
3. Basic infection workup (chest x-ray, urinalysis, paracentesis to exclude SBP if ascites
present, possibly blood cultures)
4. Review medication list
5. CT to exclude alternative pathology
a) Pts with a history of HE are prone to falls ([Link] hematoma), so there should be
a low threshold to obtain a CT scan
b) For pts who develop encephalopathy within hospital ([Link] GI bleeding),
neuroimaging has lower yield

Diagnosis :
1. There is no test which can prove the presence of HE (diagnosis of exclusion). Exclude
other DD especially subdural hematoma, meningitis or encephalitis, hypoglycemia,
alcohol intoxication or withdrawal, wernicke encephalopathy. The closest we have to a
definitive test for HE is improvement following therapy, but even this isn’t 100% specific
since many forms of metabolic encephalopathy will improve with supportive care
2. HE may often coexist with other causes of delirium. Thus, discovering one cause of
delirium ([Link]) doesn’t necessarily exclude coexisting HE.

Therapy :
1. Cathartic : one or both of the following
a) Lactulose start 30 ml q2-4h, titrate to >4 bowel movements per day
b) Fleet enema
2. Non-absorbable antibiotics : rifaximin 550 mg BID (initiate immediately)
3. Aggresive treatment for any precipitants or coexisting problems :
a) Treat any coexisting infection
b) Follow electrolytes and correct if there is abnormality (esp sodium and potassium
abnormalities)
- Hypo or hypernatremia. Lactulose as an osmotic cathartic agents removes water
from the body and leads to hypernatremia. Hyponatremia is also a common feature
of cirrhosis.
- Hypokalemia may increase renal ammoniagenesis and ammonia reabsorption
c) Treat any coexisting renal failure (may include therapy for hepatorenal syndrome)
- Rehydration, do not diuresis (avoid volume depletion)
- Consider renal replacement therapy if renal function keeps worsen
4. Avoid any long-acting neuroactive or delirium-causing medication (for intubated pts only
use propofol or dexmedetomidine). Avoid benzodiazepine, opioid, antipsychotics.
5. Nutrition : do not restrict protein intake