Acute liver failure

A 22-year-old woman with recent history of dental pain presents to the ED after being found lethargic and exhibiting altered mental status following ingestion of an entire bottle of acetaminophen over the preceding 3 days. Her roommate thinks she ingested around 20 500-mg tablets in the preceding 24 hours alone. Liver laboratory values are notable for aspartate aminotransferase (AST), 10,000 U/L; alanine aminotransferase (ALT), 11,530 U/L; total bilirubin, 2.5 mg/dL; and international normalized ratio (INR) 2.2. On examination, the patient appears somnolent and demonstrates asterixis. GENERAL FEATURES Acute liver failure (ALF) is severe acute liver injury due to an underlying insult or illness lasting fewer than 26 weeks, in the absence of underlying liver disease or cirrhosis, with impaired liver synthetic function (INR ≥ 1.5) and physical examination findings of encephalopathy. ALF is associated with high morbidity and mortality, requiring ICU-level care and prompt referral to a tertiary care center with liver transplantation capabilities. Causes of ALF include viral hepatitis, drug-induced hepatitis, hypoxic liver injury, Budd-Chiari syndrome, autoimmune hepatitis, acute fatty liver of pregnancy, HELLP syndrome, liver infiltration by tumor, toxic mushroom ingestion (Amanita phalloides), sinusoidal-obstruction syndrome, ischemic hepatitis, hemophagocytic lymphohistiocytosis, and Wilson disease. Nearly half of ALF cases in the United States are due to drug-induced hepatitis (most commonly acetaminophen). Acute infection with hepatitis B virus can cause ALF, as can hepatitis B virus reactivation in patients on immunosuppressive therapy (eg, chemotherapy, rituximab). Viruses less commonly implicated in ALF: herpes simplex virus (HSV), cytomegalovirus, Epstein-Barr virus, adenovirus, varicella-zoster virus (VZV), and parvovirus. Commonly, hepatocyte necrosis leads to liver synthetic dysfunction in ALF. ALF can cause neurologic impairment or death, due to acute hyperammonemia, astrocyte swelling, cerebral edema, increased intracranial pressure, and herniation. Patients with ALF are at high risk for infection (eg, pneumonia, urinary tract infection, bacteremia, fungemia) and multiorgan dysfunction (eg, cardiovascular, pulmonary, renal, and neurologic). Survival without liver transplantation in ALF varies depending upon cause, age, and other factors, but overall transplant-free survival is approximately 50%. CLINICAL ASSESSMENT Obtain medical history including medications (prescription, OTC, herbal and other supplements), toxin exposures, travel history, and family history. Patient may present with fatigue, nausea, vomiting, jaundice, right upper abdominal pain, abdominal distension, easy bruising or bleeding, or edema. Assess for encephalopathy, including somnolence, impaired concentration, asterixis, or milkmaid grip. DIAGNOSIS Liver biopsy is infrequently needed, but may be help determine etiology of ALF if unclear. Discuss with or consult hepatology. Send initial laboratory workup: hepatic function panel, basic metabolic panel, prothrombin time/INR, complete blood cell count, arterial ammonia, and arterial blood gas or venous blood gas. Trend these laboratory testing results every 1 to 2 hours. Send serum acetaminophen level and serum/urine toxicology. Send autoimmune workup (ANA, AMA, quantitative immunoglobulins), viral workup (HAV IgM, HBsAg, anti-HBc IgG and IgM, HBV PCR, HCV Ab, HCV PCR, anti-HEV IgM [if endemic], HSV PCR, VZV PCR, CMV PCR), and metabolic evaluation (ceruloplasmin). Send broad infectious workup (blood cultures, urinalysis, urine culture, chest radiograph). Send two type and screen blood tests, HIV 1/2 screen, and beta HCG for liver transplant evaluation. AST and ALT can rise above 1,000 with hepatocellular injury. Rising total bilirubin and INR suggest worsening liver synthetic function. Serum ammonia level elevation, thrombocytopenia, hypoglycemia, acute kidney injury, hypokalemia, and hypophosphatemia can occur. Abdominal imaging (ultrasound, CT) can assess for underlying liver disease (eg, cirrhosis) or signs of portal hypertension (eg, splenomegaly, ascites, varices, portal venous thrombosis). Neuroimaging (brain CT, MRI) can rule out central neurologic etiologies of altered mental status and assess for cerebral edema. Box 1TREATMENT Obtain IV access for fluids, medications, and vasopressors as needed; goal mean arterial pressure of 75 mm Hg or higher. Consider empiric antibiotics if concern for infection or hemodynamic instability. Consider intubation if worsening encephalopathy and inability to protect airway. Renal replacement therapy manages hyperammonemia. If any neurologic findings are concerning for cerebral edema, perform STAT noncontrast head CT and consider starting hypertonic saline. Optimize nutrition early (goal of 1 to 1.5 g protein/kg body weight/day). Enteric route is best if possible. Treatment varies by cause. Acetaminophen ingestion: activated charcoal within 4 hours and/or N-acetylcysteine as soon as possible Pregnancy-related causes (HELLP, acute fatty liver of pregnancy): delivery of baby Autoimmune hepatitis: IV methylprednisolone A. phalloides poisoning: gastric lavage, activated charcoal, and IV penicillin G Wilson disease: consider liver transplant Budd-Chiari syndrome: consider transjugular intrahepatic portosystemic shunt (TIPS) and/or anticoagulation HSV or VZV hepatitis: IV acyclovir Viral hepatitis B: entecavir or tenofovir Urgent hepatology consult and referral and consideration of transfer to medical center with liver transplant capabilities CASE CONCLUSION The patient is diagnosed with ALF secondary to acetaminophen overdose, presenting with encephalopathy and markedly elevated liver enzymes. She undergoes prompt evaluation and management, including neuroimaging and hepatology consultation, and is ultimately referred for possible liver transplantation due to the severity of her condition.Box 2