Liver Failure, Acute

These correspond to diseases that can cause LFTs in the 1000s, which actually carries a fairly limited differential diagnosis:

1. Drugs/toxins:

Acetaminophen - accounts for the majority of cases in the US.
Other drugs/toxins including isoniazid, antibiotics, anticonvulsants, PTU, and poison mushrooms.
Importantly, alcohol does not really cause LFTs in the 1000s nor does it cause acute liver failure!!!

2. Acute Viral hepatitis:

Hep B > Hep A, not really Hep C. Also Hep D (with Hep B coinfection) and Hep E (esp pregnant women).
Rarely, other viruses such as HSV, CMV, adenovirus, and others can cause ALF especially in immunocompromised patients.

3. Vascular: "Shock liver" from extreme hypotension, Budd-Chiari, Veno-occlusive disease

4. Metabolic:

Wilson's Disease - accounts for 2-3% of ALF - presents usually in young adults with hemolytic anemia and acute liver failure, often with characteristically low Alk Phos.
Other metabolic causes include complications related to pregnancy - Acute Fatty Liver of Pregnancy and HELLP syndrome.
Reye's syndrome - associated with children taking ASA while suffering from viral illness (influenza, varicella).

5. Autoimmune Hepatitis - often is the first presentation, can be fulminant.

Overview of ALF Manifestions and Basic Management
1. Neuro - Hepatic Encephalopathy, Cerebral Edema, Seizures.

Cerebral edema is common in severe encephalopathy and is a major cause of death in acute liver failure (the other common cause of death is sepsis). Unclear pathophysiology but likely related to osmotic derangements in astrocytes, alterations in cerebral blood flow, and other hand-waving theories.
Management involves raising the head of the bed, hyperventilation (low PCO2 à cerebral vasoconstriction), mannitol (hyperosmolar solution and osmotic diuresis leading to plasma hyperosmolarity and hypernatremia), hypertonic saline. Induced hypothermia is also an experimental therapy but is not yet routinely done (has risks of coagulopathy, infection risk, and arrhythmias).
Routine use of invasive ICP monitoring is controversial and is done at some transplant centers, not at Stanford. Main options are intraventricular monitoring (aka EVD) which can also help with therapy (removing CSF) - the gold standard, vs subarachnoid “bolt” – more commonly done, as EVD placement is more dangerous in these coagulopathic patients.

2. CV –Hypotension – get loss of vascular tone leading a low SVR state (distributive shock) that resembles sepsis. Due to evil humors including increased nitric oxide.

3. Pulmonary – often get infections as well as ARDS, whether due to iatrogenesis (i.e. TRALI) or from evil humors is often unknown.

4. Renal – Acute renal failure, often due to Hepatorenal syndrome. Also, severe electrolye abnormalities (hyponatremia, hypophosphatemia, hypokalemia, hypomagnesemia, also metabolic acidosis). Patients often need CVVH.

5. GI – besides liver failure, another important GI issue is severe malnutrition – early feeding is very important. Also, GI bleeding is common due to coagulopathy/thrombocytopenia.

6. Heme – severe coagulopathy – can be just from lack of production of clotting factors from liver, also DIC is common. Also get thrombocytopenia and anemia.

7. ID – pts are highly susceptible to infections – due to impaired WBC function, decreased hepatic production of complement, gut translocation, and need for invasive procedures (CVCs, etc). Basically, have very low threshold for broad spectrum abxs and antifungals. These patients develop sepsis like it is nothing.

8. Endo – hypoglycemia is very common and severe, due to poor nutrition and impaired hepatic gluconeogenesis.

(Chanu Rhee MD, 10/25/10)