Acute liver failure

Question 1

General findings

Answer 1

Rapidly worsening liver function resulting in coagulopathy and hepatic encephalopathy
Fulminant liver failure: onset of hepatic encephalopathy within 8 weeks of initial symptoms (e.g., jaundice)
Subacute liver failure: onset within ≤ 26 weeks

Question 2

Etiology

Answer 2

✔Drugs/toxins
Acetaminophen toxicity (most common) (ALT usually over 1000 units)👓
Phenytoin, halothane, isoniazid
Amanita phalloides 
Aflatoxin 
Further risk factors: alcohol, cocaine 

✔Viral hepatitis: hepatitis A, B, E, or B + D, CMV (Most common viral cause is HBV, accounts for 8%)
Vascular disorders: Budd-Chiari syndrome, ischemic hepatitis
Pregnancy-related: HELLP syndrome, acute fatty liver of pregnancy 👓
Others: Hypoperfusion, sepsis, autoimmune hepatitis, Wilson’s disease!

Question 3

Clinica

Answer 3

Jaundice
Signs of hepatic encephalopathy: altered mental state, asterixis
Symptoms of cerebral edema: nausea, vomiting, confusion

Question 4

Diagnosis

Answer 4

-Laboratory findings: ↑ PT with INR ≥ 1.5, often ↑↑ ALT and AST, ↑ bilirubin level, and platelet count ≤ 150,000/mm3

Further diagnostics: depending on the suspected underlying cause
Viral serologies
!Toxicology screening (e.g., acetaminophen level)
Autoimmune hepatitis serology
RUQ abdominal ultrasound

Question 5

Treatment

If HELLP syndrome, induction of delivery is required!

Answer 5

✔Early transfer to a liver transplant center💥

✔Intravenous N-acetylcysteine! (The most common indication for NAC is acetaminophen overdose. It has also been shown to improve transplant-free survival even in patients with non-acetaminophen-related acute liver failure).👓

✔Address/prevent complications: e.g., SIRS, cerebral edema, ICH, encephalopathy, coagulopathy, renal failure, and infection (e.g. fluid managment

✔Address underlying cause: e.g., antiviral treatment for hepatitis B, steroids for autoimmune hepatitis, or delivery for HELLP syndrome!

Liver transplantation is the only therapeutic option for patients without sufficient regeneration of hepatocytes.
Prognosis: The mortality rate without liver transplantation ranges from 30% (acetaminophen toxicity) to 80% (non-acetaminophen-related liver failure).

1.Goals of management of early encephalopathy (I-II):

Hypoglicemia, bleeding, hypoxemia and salt equilibrium can worsen encephalopathy and should be managed. Overhydratation should be avoided because can increase ICP. Somministration of lactulose is required (non a dosi elevate perchè la diarrea concomitante può indurre disidratazione con iponatremia e quindi edema citotossico ma anche ipokalemia con peggioramento della encefalopatia)

2.Late stages (III-IV) (il soggetto è bradicardico con ICP elevata, è il riflesso di Cushing) (pupillar dilatation and decerebrate posturing are often present)

Intubation for air protection is required, so the use of sedation and vasopressor is required. PROPOFOL has been suggested for sedation because it may reduce cerebral blood and so ICP

NB Factors that increase ICP should be avoided shuch as PEEP (e inoltre riduce la perfusione eoatica) , frequent movements, fevere, arterial hypertension,coughing, seizures. Monitorare ICP mediante device subdurali o intraparenchimali aumenta il rischio di bleeding e infezioni.
L’obiettivo è ridurre la ICP al di sotto di 20 mmHg

• Per le seizures, indicata la FENITOINA.
• Mannitol for ICP. has been dimostrated to improve survival by reducing cerebral edema.
• Hyotermia (riduce il metabolismo, riduce il flusso cerebrale e quindi ammonia intake)
• fluid resuscitation with normal saline and vasopressor to maintain mean arterial pressure of 60/74 mmHg
• fresh frozen plasma or replacement therapy only if hemorrage or prior to invasive procedure.
• PPi for stress ulcer (to prevent bleeding)
• colloids in pre-epatorenal syndrome with octreotide