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="" alt="" and="" reducing="" span="" 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 abdominal="" but="" careful="" causing="" distension="" embarassment="" gaseous="" of="" respiratory="" span="">

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 mannitol="" no="" of="" prophylactic="" role="" span="">

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 invasive="" mm3="" or="" procedures="" span="">

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="" adequate="" following="" irrespective="" of="" resuscitation="" span="" volume="">

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