Fulminant Hepatic Failure

OVERVIEW

Fulminant Hepatic Failure = rapid onset of encephalopathy in conjunction with hepatic synthetic failure.

CAUSES (DAVES)

• Drugs – paracetamol, idiosyncratic, illicit, herbal/alternative (amanita mushroom), halothane
• Alcohol
• Viruses – HAV, HBV +/-D, HCV, HEV, CMV, EBV, HSV
• Extras – acute fatty liver of pregnancy, HELLP, toxins, ischaemic necrosis, vascular, metabolic, autoimmune, Wilson’s disease, Budd-Chiari, post hepatic surgery, idiopathic
• Sepsis

HEPATIC ENCEPHALOPATHY

• sleep disturbance
• asterixis
• hyperreflexic
• can be hemiplegic

Precipitating factors:

• GIH
• infection
• hypokalaemia
• sedatives
• increased protein intake
• progressive hepatic dysfunction
• renal failure

Types:

• A = acute liver failure
• B = presence of portocaval shunting
• C = in context of cirrhosis

Grade I -> IV

• mildly drowsible but rousable and coherent
  -> responding to pain/unconscious

INVESTIGATIONS

• elevated ammonia (not required to make diagnosis of encephalopathy)
• urine and serum toxicology screen
• hepatitis serology
• ceruloplasmin
• antinuclear antibodies
• smooth-muscle antibodies
• serum protein electrophoresis
• CMV and EBV serology
• serum phosphate: decrease suggestive of hepatocyte recovery and regeneration -> good prognostic marker

MANAGEMENT

Resuscitation

A – intubated if unresponsive from encephalopathy (RSI to prevent aspiration)
B – often have respiratory failure from pleural effusions and may have aspirated requiring mechanical ventilation
C – fluid maintenance, often have a hyperdynamic circulation, vasoactive medication
D – monitoring for intra-cranial hypertension: ICP bolt, mannitol, propofol, thiopentone, moderate hypothermia (32-33 C), hypertonic saline

• Once stabilized early consultation with Liver Transplant Centre
• Vigilant monitoring for infection (bacterial, fungal)

Specific treatment

• paracetamol OD: N-acetylcysteine 150mg/kg LD, 50mg/kg over 4 hours, 100mg/kg over 16 hours
• Amanita poisoning: penicillin
• acute fatty liver of pregnancy: delivery of infant and placenta
• Wilson’s disease: zinc and trientine therapy, apheresis
• Acute Budd-Chiari: TIPS, surgical decompression, thrombolysis -> transplantation
• HSV: acyclovir
• ischaemic: restore circulation to liver
• encephalopathy:
  — lactulose -> increases ammonia elimination
  — metronidazole -> alter gut flora to decrease ammonia production
  — flumazenil (controversial)
• coagulopathy:
  only treat with FFP if bleeding or prior to procedures
  — FVIIa safe and effective
  NAC:
  — continue until encephalopathy resolves
• TIPS procedure (see TIPS)
• short-term extracorporeal hepatic support (see MARS)

Criteria for Transplantation (King’s College Criteria)

Paracetamol induced fulminant hepatic failure

• pH < 7.3 or INR > 6.5 (PT > 100s)
  +
• Cr > 300micromol/L
  +
• grade III or IV encephalopathy

Non-paracetamol induced fulminant hepatic failure

• INR > 6.5 (PT > 100s) or any 3 of the following variables:

(1) age < 10 or > 40 yrs
(2) aetiology – non A, non B hepatitis, halothane hepatitis, idiosyncratic drug reactions
(3) duration of jaundice before encephalopathy > 7 days
(4) INR > 3.5 (PT > 50s)
(5) bilirubin > 300micromol/L

General treatment

• electrolyte balance (hypokalaemia, hyponatraemia, hypophosphataemia)
• Na+ restriction + diuretics -> decreases ascites
• frequent glucose monitoring (hypoglycaemia)
• nutrition (amino acids, lipids, glucose, essential elements)
• renal failure is common (especially in paracetamol OD -> direct renal toxic effects)
• feed

Disposition

• management in ICU
• early discussion with liver transplant unit (prior to reversal of coagulopathy)
• discussion with family (high mortality)

COMPLICATIONS

• cerebral oedema and herniation
• coagulopathy
• GI bleed
• sepsis
• renal failure
• hypoglycaemia
• electrolyte abnormalities
• respiratory failure: impaired ventilation c/o coma, pleural effusions, ARDS, intra-pulmonary shunts, aspiration, sepsis

CONTROVERSIAL ISSUES

• targeted CPP management with insertion of an ICP monitor
• MARS therapy
• use of FVIIa

References and Links

Journal articles

• Craig DG, Lee A, Hayes PC, Simpson KJ. Review article: the current management of acute liver failure. Aliment Pharmacol Ther. 2010 Feb 1;31(3):345-58. PMID: 19845566.
• Laleman W, Verbeke L, Meersseman P, Wauters J, van Pelt J, Cassiman D, Wilmer A, Verslype C, Nevens F. Acute-on-chronic liver failure: current concepts on definition, pathogenesis, clinical manifestations and potential therapeutic interventions. Expert Rev Gastroenterol Hepatol. 2011 Aug;5(4):523-37; quiz 537.PMID: 21780899.
• Lee WM. Recent developments in acute liver failure. Best Pract Res Clin Gastroenterol. 2012 Feb;26(1):3-16. PMC3551290.
• Patton H, Misel M, Gish RG. Acute liver failure in adults: an evidence-based management protocol for clinicians. Gastroenterol Hepatol (N Y). 2012 Mar;8(3):161-212. PMC3365519.
• Saliba F, Samuel D. Acute liver failure: Current trends. J Hepatol. 2013 Apr 6. PMID: 23567082.