GASTROENTEROLOGY
ACUTE LIVER FAILURE
Definition
• Acute hepatic disease + coagulopathy + encephalopathy; w/o known pre-existing liver dis.
• Fulminant = develops w/in 8 wk; subfulminant = develops between 8 wk and 6 mo
Etiology (Lancet 2010;376:190)
• Viral (12% of cases)
HAV, HBV, HCV (rare), HDV + HBV, HEV (esp. if pregnant)
HSV (immunosupp Pt), EBV, CMV, adenovirus, paramyxovirus, parvovirus B19
• Drugs/toxins (nearly 80% of cases; Hep 2010;52:2065)
Drugs: acetaminophen (most common cause; >40% of all cases), phenytoin, INH, rifampin, sulfonamides, tetracycline, telithromycin, amiodarone, PTU, valproate
Toxins: fluorinated hydrocarbons, CCl4, Amanita phalloides
• Vascular: ischemic hepatitis, Budd-Chiari syndrome, hepatic SOS, malignant infiltration
• Autoimmune hepatitis (initial presentation)
• Misc.: Wilson’s, acute fatty liver of pregnancy (HELLP, Reye’s), idiopathic (up to 20%)
Clinical manifestations
• Initial presentation usually nonspecific, w/ nausea, vomiting, malaise, followed by jaundice
• Neurologic
encephalopathy: stage I = DMS; 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 → ↑ ICP, ↓ 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 (↓ clotting factors, ↓ plt, DIC), pancreatitis (? due to ischemia)
• Renal: ATN, hepatorenal syndrome, hyponatremia, hypokalemia, hypophosphatemia
• Hematology: coagulopathy (due to ↓ synthesis of clotting factors ± DIC)
• Infection (~90% of Pts): esp. with Staph, Strep, GNRs and fungi (↓ immune fxn, invasive procedures); SBP in 32% of Pts; fever and ↑ WBC may be absent
• Endocrine: hypoglycemia (↓ glc synthesis), metabolic acidosis (↑ lactate), adrenal insuf.
Workup (Hep 2012;55:965)
• Viral serologies (see “Acute Hepatitis Workup”)
• AIH serologies, ceruloplasmin & serum/urine copper, pregnancy test, arterial NH3
• Toxicology screen (acetaminophen levels q1–2h until peak determined)
• Imaging studies (RUQ U/S or abd CT, Doppler studies of portal and hepatic veins)
• Liver biopsy (unless precluded by coagulopathy → in which case consider transjugular)
Treatment (Hep 2012;55:965)
• ICU care at liver transplant ctr for hemodynamic & ventilatory support; CVVH for ARF
• IV N-acetylcysteine (same dose as for acetaminophen): all Pts w/ hepatic failure and grade 1–2 enceph: ↑ cerebral blood flow and ↑ transplant-free survival (Gastro 2009;137:856)
• Cerebral edema: rare w/ NH3 <75 mM/L, invariable if >200 mM/L; consider ICP monitoring if stage III/IV enceph; if ↑ ICP → mannitol 0.5–1.0 mg/kg; prophylactic 3% saline for goal Na 145–155 mEq/L if NH3 >150 mM/L, grade 3/4 enceph, ARF or on vasopressors; barbiturates & hypothermia if ↑ ICP refractory to osmotic agents
• Encephalopathy: intubate for grade III or IV; lactulose (avoid diarrhea & overdistension)
• Coagulopathy: vit K; FFP/plts/cryo if active bleeding; ? recomb. factor VIIa; PPI prophylaxis
• Infection: low threshold for abx (broad spectrum, eg, vancomycin & 3rd-gen ceph.), albeit no proven mortality benefit to empiric abx
• Treatment of specific causes: nucleo(s/t)ides for HBV; steroids for AIH; consider plasma exchange for Wilson’s; IV acyclovir for HSV; gastric lavage & PCN-G for Amanita phalloides; delivery of child for pregnancy related; TIPS and anticoag for Budd-Chiari
• Liver transplantation if poor prognosis w/ grade II or III encephalopathy (see below)
Prognosis
• Non-acetaminophen ALF mortality ~80%, acetaminophen-induced ALF mortality ~30%
• Predictors of poor outcome
Acetaminophen-induced: pH <7.3 after fluids or INR >6.5, Cr >3.4, or grade III/IV enceph.
Non-acetamin.-induced: INR >6.5 or 3 of the following: non-A/B viral hep; other drug toxicity; time from jaundice to enceph. >7 d; age <10 or >40 y; INR >3.5; Tbili >17.4
• ALFED model: NH3, Tbili, INR, & ≥2 enceph (Gut 2012;61:1068) & ALFSG index: coma grade, INR, Tbili, PO4, & serum CK18 (Gastro 2012;143:1237) are new indices for predicting need for liver Tx and mortality
• ~25–30% of Pts w/ ALF undergo liver transplantation w/ 5-y survival rate of 70%