Acute Liver Failure

Definition

• Acute hepatic disease • coagulopathy • encephalopathy

• Fulminant develops w in 8 wks; subfulminant develops between 8 wks and 6 mos

Etiology

HAV. HBV. HCV (rare). HDV ♦ HBV. HEV (especially if pregnant)

HSV (immunocompromised Pt). EBV. CMV. adenovirus, paramyxovirus, parvovirus B19

Drugs: acetaminophen (most common cause; 40% of all cases), phenytoin. INH.

rifampin, sulfonamides, tetracycline, telithromycin. amiodarone. PTU Toxins: fluorinated hydrocarbons. CCI«. Amanita phalloides

• Vascular: ischemic hepatitis. Budd-Chiari syndrome, hepatic SOS. malignant infiltration

• Autoimmune hepatitis (usually initial presentation)

• Misc.: Wilson's disease, acute fatty liver of pregnancy. HELLP. Reyes syndrome

Clinical manifestations

• Initial presentation usually nonspecific, w nausea, vomiting, malaise, followed by jaundice

• Neurologic encephalopathy: stage I aMS; stage II lethargy, confusion; stage III stupor: stage IV coma asterixis in stage I II III encephalopathy, hyperreflexia. clonus, rigidity in stage III IV cerebral edema — ÎICP. i CPP — cerebral hypoxia, uncal herniation, Cushing's reflex (hypertension • bradycardia), pupillary dilatation, decerebrate posturing, apnea

• Cardiovascular: hypotension with low SVR

• Pulmonary: respiratory alkalosis, impaired peripheral O2 uptake, pulm edema. ARDS

• Gastrointestinal: GIB (1 clotting factors. I pits. DIC, fibrinolysis), pancreatitis (? hypoxia)

• Renal: ATN. hepatorenal syndrome, hyponatremia, hypokalemia, hypophosphatemia

• Hematology, coagulopathy (due to i synthesis of clotting factors • DIC)

• Infection ( 90%): especially with Staph, Strep, GNRs, and fungi (i immune fxn, invasive procedures); SBP in 32% of Pts; fever and ' WBC may be absent

• Endocrine: hypoglycemia (i glc synthesis), metabolic acidosis (Î lactate)

Workup

• Viral serologies

• Toxicology screen (acetaminophen levels q1-2h until peak determined)

• Imaging studies (RUQ U S or abd CT. Doppler studies of portal and hepatic veins)

• Other tests: autoimmune serologies, ceruloplasmin and urine copper

• Liver biopsy (unless precluded by coagulopathy in which case consider transjugular)

Treatment

• ICU care at liver transplant center to provide hemodynamic & ventilatory support.

CVVH for ARF. D10 drip for hypoglycemia, etc.

• Cerebral edema: consider ICP monitoring (stage III IV enceph); head of bed -30°.

hyperventilation, mannitol. barbiturates. ? induction of hypothermia

• Coagulopathy SC IV vit K; FFP pits cryopreciprtate if active hemorrhage; ? rec factor Vila

• Infection: low threshold for abx (broad spectrum; IV vancomycin & 3rd-gen ceph.)

• Treatment of specific causes: N-acetylcysteine for acetaminophen, corticosteroids for autoimmune hepatitis, chelation therapy for Wilson's disease. IV acyclovir for HSV. gastric lavage and charcoal • penicillin and silymarin for Amanita phalloides

• If unclear etiology acetaminophen levels unreliable, esp in cases w unintentional OD

(Coitro 2006:130:687); low threshold for NAC Rx (regardless of acetaminophen levels)

• Liver transplantation if poor prognosis (see below)

• Extracorporeal liver assist devices under evaluation as "bridge" to transplant

Prognosis

• Predictors of poor outcome (Castro 1989:97:439)

age <10 or >40 y cause other than acetaminophen. HAV, or HBV grade III or IV encephalopathy (onset >7 d after onset of jaundice) PT >50. bilirubin >17.5

• Liver transplantation 1-y survival rate -60%

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