Acute Liver Failure
Definition:
INR at least 1.5 AND
any degree of mental alteration
in a patient without preexisting cirrhosis and with an illness of less than 26 weeks duration.
OR
if cirrhosis is present in Wilson disease, vertically-acquired HBV or autoimmune hepatitis, can also be included if their disease has only been recognized for less than 26 weeks.
Initial Lab Investigations:
Prothrombin time/INR
Chemistries: sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphate, glucose
LFT: AST, ALT, alkaline phosphatase, GGT, total bilirubin, albumin
RP: creatinine, blood urea
Arterial blood gas
Arterial lactate
Full blood count
Blood type and screen
Acetaminophen level
Toxicology screen
Viral hepatitis serologies: anti-HAV IgM, HBSAg, anti-HBc IgM, anti-HEV, anti-HCV, anti-HDV
Ceruloplasmin level
Pregnancy test (females)
Ammonia (arterial if possible)
Autoimmune markers: ANA, ASMA, Immunoglobulin levels
HIV status
Specific etiologic treatment
Paracetamol: NAC may be administered intravenously (loading dose is 150 mg/kg in 5% dextrose over 15 minutes; maintenance dose is 50 mg/kg given over 4 hours followed by 100 mg/kg administered over 16 hours). Then 150 mg/kg administered over 24 hours infusion till INR <1.5 and ALT reducing trend
Mushroom: penicillin G and silymarin
Hep A and C: Supportive rx
Hep B: NA is purely supportive
Herpes / varicella zoster: Acyclovir
Wilson’s: Transplant
AIH: High dose steroids
Ischaemic hepatitis: Cardiovascular support
AFLP/ HELLP: Delivery
Budd Chiari: Transplant if malignancy ruled out
General considerations:
Any altered mental status warrants ICU care
Cerebral oedeoma often occurs due to osmotic disturbances, loss of autoregulation, hypoxia. Rarely in HE Grade I-II but by Grade III (25-35%) and Grade IV (65-75%)
Lactulose to reduce ammonia because level > 200microgm/dL is a/w cerebral herniation
Summary of treatment:
Cerebral Edema/Intracranial Hypertension
Grade I/II Encephalopathy:
Consider transfer to liver transplant facility and listing for transplantation
Brain CT: rule out other causes of decreased mental status; little utility to identify cerebral edema
Avoid stimulation, avoid sedation if possible, nurse in quiet environment
Antibiotics: surveillance and treatment of infection required with regular blood and urine cultures with CXR; prophylaxis possibly helpful, use SIRS criteria. Low threshold for antibiotics and antifungal
Lactulose: possibly helpful to reduce ammonia <200 but careful of abdominal gaseous distension causing respiratory embarassment
IV NAC can also be considered at this stage
Grade III/IV Encephalopathy:
Continue management strategies listed above
Intubate trachea (may require sedation)
Sedation during tracheal suction to avoid stimulation
Elevate head of bed 30 degree
Consider placement of ICP monitoring device
Immediate treatment of seizures if present is required; prophylaxis of unclear value but autopsy show less cerebral oedema
Mannitol: use for severe elevation of ICP or first clinical signs of herniation (unequal pupils, oval pupils, hyperreflexia, hypertonia, upgoing plantar, clonus) Dosage 0.5 – 1g/kg, can repeat if serum osmolality <320mosm/L. No role of prophylactic mannitol
Hyperventilation: effects short-lived; may use for impending herniation (PaCO2 25-30mmHg)
Hypertonic saline: upto 30% to maintain S. Na level between 145 – 155
Barbiturate as last resort but severe hypotension can occur
Hypothermia (32 -34 celcius)
Steroids is not useful
Infection
Surveillance for and prompt antimicrobial treatment of infection required
Antibiotic prophylaxis possibly helpful but not proven
Use SIRS criteria
Coagulopathy
Vitamin K: give at least one dose
FFP: give only for invasive procedures or active bleeding.
Platelets: give for platelet counts <10,000/mm3 or invasive procedures
Recombinant activated factor VII: possibly effective for invasive procedures
Prophylaxis for stress gastric / duodenal ulceration: give PPI
Hemodynamics/Renal Failure
Pulmonary artery catheterization
Volume replacement
Pressor support (dopamine, epinephrine, norepinephrine) as needed to maintain adequate mean arterial pressure
Avoid nephrotoxic agents
Continuous modes of hemodialysis if needed rather than intermittent
NAC, prostacyclin: effectiveness unknown
Vasopressin: not helpful in ALF; potentially harmful.
Metabolic Concerns
Follow closely: glucose, potassium, magnesium, phosphate, calcium must be normal level
Consider nutrition: enteral feedings if possible or total parenteral nutrition if not
Transplant criteria
King’s College Criteria:
Acetaminophen-induced ALF:
Arterial pH <7.3 (following adequate volume resuscitation) irrespective of
coma grade
OR
PT >100 seconds (INR _ 6.5) AND
serum creatinine _300 _mol/L AND
grade III / IV coma
Non-acetaminophen-induced ALF:
PT >100 seconds irrespective of coma grade
OR
Any three of the following, irrespective of coma grade:
– Drug toxicity, indeterminate cause of ALF
– Age < 10 years or > 40 years
– Jaundice to coma interval > 7 days
– PT > 50 seconds (INR > 3.5)
– Serum bilirubin > 300 mmol/L
Hepatic Encephalopathy Stages
- Grade I: sleep disturbances, restlessness, mood fluctuations, loquacity (talkativeness), impaired attention/concentration
- Grade II: asterixis, ataxia, changes in reflexes (usually diminution), dysarthria
- Grade III: increasingly sleepy but arousable, ,aggressive behaviour, monotonous voice, perseverations, increased reflexes, clonic spasm, pyramidal symptoms, increased muscle tone
- Grade IV: comatose