Acute liver failure: A progress report

Table 1 Characteristics of subgroups of patients with acute liver failure

Characteristics	Hyperacute liver failure	Acute liver failure	Subacute liver failure
Encephalopathy	Yes	Yes	Yes
Duration of jaundice	0-7 d	8-28 d	29-72 d
Cerebral edema	Common	Common	Seldom
Prothrombin time	Prolonged	Prolonged	Least prolonged
Bilirubin	Slightly elevated	Elevated	Elevated
Prognosis	Moderate	Poor	Poor

Table 2 Principal causes of acute liver failure

Causes	Agents responsible
Viral hepatitis	Hepatitis A, B, C, D, E, or F (?) virus
	Herpes simplex virus
Drug related liver injury	Epstein-Barr virus, Cytomegalovirus
Toxins	Adenoviruses, Paramyxovirus
Vascular events	Acetaminophen
Miscellaneous	Idiosyncratic reactions
	Drug-induced steatosis
	Carbon tetrachloride
	Amanita phalloides
	Phosphorus
	Ischemia or shock
	Veno-occlusive disease
	Heat stroke and Hypothermia
	Malignant infiltration
	Wilson's disease
	Acute fatty liver of pregnancy
	Reye's syndrome, Cryptogenic

Table 3 Drugs implicated in idiosyncratic acute liver failure

Infrequent causes	Rare causes	Synergistic causes
Isoniazid	Carbamazepime	Alcohol and acetaminophen
Valproate	Ofloxacin	Trimethoprim and sulfamethoxazole
Halothane	Ketoconazole	Rifampin and isoniazid
Sulfonamides	Niacin	Amoxicillin and clavulanic acid
Propylthiouracil	Labetalol
Aiodarone	Etoposide (VP-16)
Disulfiram	Imipramine
Dapsone	Interferon alfa
	Flutamide

Table 4 Possible predisposing factors for acute liver failure

Etiologic agents
Viruses	various hepatotropic viruses
	superinfection of hepatotropic viruses
	variants of a hepatotropic virus (mutants)
Chemicals
Miscellaneous
Host factors
Hyperfunction of cellular immunity
Hyperfunction of antibody production → immune complexes
Endogenous endotoxemia
Deficient phagocytosis of reticuloendothetial system
Activation of macrophages	overproduction of TNF-α and IL-1
	release of leukotrienes
	release of superoxides
Liver regeneration failure	overproduction of regeneration-suppressing factors
	disorders in cell receptors and signal transduction
Apoptosis

Table 5 Management of complications of acute liver failure

Hypoglycemia	(10%) dextrose continuous infusion
	Bolus (50%) dextrose solution
Encephalopathy	Lactulose per NG enemas
	Neomycin/metronidazole/polymycin B
	GI therapy + branched chain amino acids	prostaglandins
		plasma exchange
	Rule out sepsis, GI bleeding	hypoxia, drug effects
		hypoglycemia, acid-base imbalance
Cerebral edema	Restrict fluids, Avoid patient stimulation
	Mannitol bolus
	Consider intracranial pressure	monitoring, thiopental infusion
Hypotension	Consider GI bleed/hypovolemia/septic shock
	Optimize cardiac filling pressure
	Dopamine ± norepinephrine infusion
Hypoxia	Endotracheal intubation, Mechanical ventilation
Sepsis	Broad-spectrum antibiotics, Consider fungal sepsis

NG: Nanograms, GI: Glycemic Index.

Table 6 Criteria for predicting death and the need for liver transplantation at King's College Hospital, London¹

Cause of ALF	Criteria
Acetaminophen poisoning	pH < 7.3 (irrespective of grade of encephalopathy) or Prothrombin time > 100 s and serum creatinine > 300 μmol/L (3.4 mg/dL) in patients with grade III or IV encephalopathy
All other causes	Prothrombin time > 100 s (irrespective of grade of encephalopathy)
	Any three of the following variables (irrespective of grade of encephalopathy): age < 10 yr or > 40 yr; liver failure caused by non-A, non-B hepatitis, halothane-induced hepatitis, or idiosyncratic drug reactions; duration of jaundice before onset of encephalopathy > 7 d; prothrombin time > 50 s; serum bilirubin > 300 mmol/L (17.5 mg/dL)

¹Transplantation was considered if the likelihood of survival was less than 20%. ALF: Acute liver failure.