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    Diagnosis and Management of
    Acute Liver Failure

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    Acute Liver Failure Overview and Diagnosis

    While acute liver failure (ALF) remains a relatively rare event, estimated at approximately 2,000 cases per year, the mortality associated with this disease is staggering.

    At California Pacific Medical Center in San Francisco, Calif., our Acute Liver Failure Program is directed by Timothy Davern, MD, an international expert in the field. While only 5% of our 1,600+ liver transplants have been due to ALF, many more patients are admitted annually for this syndrome. In 2011, of the 71 patients who underwent liver transplantation at CPMC, 9 of these patients received a transplant due to acute liver failure. At 13% of our transplant volume, this is twice the national average. Notably, there was zero mortality associated with these ALF transplants. Our program sees many more patients with acute liver injury who are managed successfully without the need for liver transplant.

    It is important to distinguish between acute hepatitis or hepatic injury and ALF:

    Acute Hepatic Injury: elevated transaminases, bilirubin, and/or INR without evidence of altered mental status (hepatic encephalopathy, HE)

    Acute Liver Failure (Fulminant): severe acute hepatic injury accompanied by coagulopathy and altered mental status (HE) Cerebral edema with subsequent herniation or sepsis with multiorgan failure are the most lethal complications of ALF. These outcomes may be prevented with earlier diagnosis and effective management. Current therapies have evolved in an effort to allow sufficient time for hepatic recovery or to perform liver transplantation if spontaneous recovery remains unlikely.

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    Causes of Acute Liver Failure

    Most frequently, ALF is the result of acetaminophen poisoning, either intentional, or often unintentional: the so-called “therapeutic misadventure.” ALF also occurs following ingestion of medications with idiosyncratic hepatotoxicity (see listing). Other less common causes of ALF include acute viral hepatitis (A, B, D, E, HSV, EBV, CMV), Budd-Chiari syndrome (hepatic vein occlusion), Amanita mushroom poisoning, Wilsons disease, or autoimmune hepatitis. Many cases remain a mystery and are classified as “seronegative” or cryptogenic.

    Medications or Supplements Implicated in ALF

    • Allopurinol

    • Alpha-methyldopa

    • Amiodarone

    • Amphetamines/Ecstasy

    • Dapsone n Diclofenac

    • Didanosine

    • Disulfiram

    • Efavirenz

    • Etoposide

    • Flutamide

    • Gemtuzumab

    • Halothane, Isoflurane

    • Imipramine

    • Isoniazid [a more common cause]

    • Ketoconazole

    • Labetalol

    • Lisinopril

    • Metformin

    • Nefazodone

    • Nicotinic acid

    • Nitrofurantoin [a more common cause]

    • Phenytoin [a more common cause]

    • Propylthiouracil [a more common cause]

    • Pyrazinamide

    • Quetiapine

    • Statins

    • Sufonamides

    • Sulfasalazine

    • Tolcapone

    • Troglitazone

    • Valproic acid

    Enhanced Toxicity:
    • Amoxicillin-clavulanate

    • Rifampin-isoniazid

    • Trimethoprim-sulfamethoxazole

    Herbal Products/Dietary Supplements:
    • Bai-Fang herbs

    • Camelia Sinensis (green tea)

    • Chaparral

    • Comfrey

    • Germander

    • Greater celandine

    • Gum Thistle

    • He Shon Wu

    • Heliotrope

    • Impila

    • Jin Bu Huan

    • Kava kava

    • LipoKinetix

    • Ma Huang

    • Pennyroyal

    • Rattleweed

    • Senecio

    • Skullcap

    • Sunnhemp

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    Early Management

    • Begin treatment immediately with N-acetylcysteine (Mucomyst®) for known or suspected ingestion of Tylenol (acetaminophen). Consider Mucomyst for all patients with ALF with grade 1-2 HE
      [Note: Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Lee WM, Hynan LS, Rossaro L, Fontana RJ, Stravitz RT, Larson AM, Davern TJ 2nd, Murray NG, McCashland T, Reisch JS, Robuck PR; Acute Liver Failure Study Group. Gastroenterology. 2009 Sep;137(3):856-64, 864.e1. Epub 2009 Jun 12.]

    • Avoid sedatives if possible

    • Assess severity/prognosis: acetaminophen level, toxicology screen/BAL, Factor V level, arterial: lactate, pH, and ammonia, AFP, phosphate, INR

    • 10% Dextrose infusion should be considered, especially for transport or documented hypoglycemia

    • Activated charcoal is recommend ed if within 4 hours of ingestion (1gm/kg orally). This will not interfere with N-acetylcysteine absorption.

    • Endotracheal intubation for grade 4 hepatic encephalopathy (HE) (consider for grade 3 with poor airway protection)

    • Measure serum osmolarity if HE or cerebral edema present or suspected. Then elevate head of bed to 30 degrees and give Mannitol 1 gm/kg IV.

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    Advanced Management

    (Not recommended without prior expertise or outside of a transplant center)

    • Intracranial pressure (ICP) monitor for known or suspected cerebral edema or intracranial hypertension (ICH)

    • Active cooling to 33-34º C with cooling blankets and ventilator for ICH not responsive to Mannitol

    • Hypertonic saline (3% NaCl) to target serum sodium to 145-150 for refractory ICH

    • Continuous renal replacement therapy (CRRT) if evidence of renal insufficiency and/or refractory ICH

    • Liver support devices—California Pacific is active in this area of research

    • Liver transplantation

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    Next Steps

    For cases in which ALF is suspected, contact our Liver Transplant Program at 415-600-1020 (hepatology). California Pacific offers a Transfer Center that is staffed round-the-clock to bring acutely ill patients to the hospital. The Transfer Center can be reached at 1-888-637-2762.
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    About California Pacific Medical Center

    California Pacific Medical Center, part of the Sutter Health NetworkOpens new window, offers kidney, pancreas, liver and heart transplantation as part of our Barry S. Levin, MD Department of Transplant.

    San Francisco Center for Liver Disease
    California Pacific Medical Center
    2340 Clay Street
    San Francisco, CA 94115
    Tel. 415-600-1020
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