Unit 4 - Acute Liver Failure

NORTHWESTERN UNIVERSITY,INC
Laoag City, Ilocos Norte
ACUTE LIVER FAILURE
I. DEFINITION
Acute liver failure (ALF) is an uncommon condition in which rapid deterioration of

the liver function results in coagulopathy and alteration in the mental status of a
previously healthy individual.
The term acute liver failure is used to describe the development of coagulopathy,
usually with an international normalized ratio (INR) of greater than 1.5, and any degree
of mental alteration (encephalopathy) in a patient without pre-existing cirrhosis and
with an illness of less than 26 weeks' duration.
Acute liver failure is a broad term that encompasses both fulminant hepatic
failure (FHF) and subfulminant hepatic failure (or late-onset hepatic failure). Fulminant
hepatic failure is generally used to describe the development of encephalopathy within
8 weeks of the onset of symptoms in a patient with a previously healthy liver.
Subfulminant hepatic failure is reserved for patients with liver disease for up to 26
weeks before the development of hepatic encephalopathy.
 West Haven Criteria (for encephalopathy)
Grade I Changes in behaviour, mild confusion, slurred speech, disordered

sleep
Grade II Lethargy, moderate confusion
Grade III Marked confusion (stupor), incoherent speech, sleeping but wakes
with stimulation
Grade IV Coma, unresponsive to pain
II. ETIOLOGY
1. Acetaminophen Hepatotoxicity
As with many drugs that undergo hepatic metabolism, the oxidative metabolite
of acetaminophen is more toxic than the drug. The highly reactive active metabolite N-
acetyl-p-benzoquinone-imine (NAPQI) appears to mediate much of the acetaminophen-
related damage to liver tissue by forming covalent bonds with cellular proteins. Ordinarily,
NAPQI is metabolized in the presence of glutathione which quenches this reactive
metabolite and acts to prevent nonspecific oxidation of cellular structures, which might
result in severe hepatocellular dysfunction.
NCM 118: Responses to Metabolic- Gastrointestinal and Liver Alteration

This mechanism fails in two different yet equally important settings. The first
is an overdose (accidental or intentional) of acetaminophen. Acetaminophen ingestion of
more than 10 g simply overwhelms the normal hepatic stores of glutathione, allowing
reactive metabolites to escape.
The second and less obvious scenario occurs in a patient who consumes alcohol
regularly. This does not necessarily require a history of alcohol abuse or alcoholism. Even
a moderate or social drinker who consistently consumes one to two drinks daily may
sufficiently deplete intrahepatic glutathione reserves. This results in potentially lethal
hepatotoxicity from what is otherwise a safe dose of acetaminophen (below the maximum
total dose of 4 g/d) in an unsuspecting individual.
2. Drug-related hepatotoxicity
Many drugs (both prescription and illicit) are implicated in the development of
fulminant hepatic failure. Drug-induced liver injury (DILI) is a leading cause of emergent
liver transplantation; in Western nations, DILI is the primary cause of acute liver failure
in adults.
Fluoroquinolones are sometimes associated with mild, transient elevations in
aminotransferase levels. In particular, moxifloxacin has been identified as presenting a risk
for acute liver failure.
Prescription medications that have been associated with idiosyncratic hypersensitivity
reactions include the following:
 Antibiotics (ampicillin-clavulanate, ciprofloxacin, doxycycline, erythromycin,
isoniazid, nitrofurantoin, tetracycline)
 Antidepressants (amitriptyline, nortriptyline)

 Antiepileptics (phenytoin, valproate) [25]
 Anesthetic agents (halothane)
 Lipid-lowering medications (atorvastatin, lovastatin, simvastatin)
 Immunosuppressive agents (cyclophosphamide, methotrexate)
 Nonsteroidal anti-inflammatory agents (NSAIDs)
 Salicylates (ingestion of these agents may result in Reye syndrome)
 Others (disulfiram, flutamide, gold, propylthiouracil)
Page 2 of 5
3. Viral Hepatitis and other viruses

Viral hepatitis may lead to hepatic failure. Hepatitis A and B account for most of these
cases. In the developing world, acute hepatitis B virus (HBV) infection dominates as a cause
of fulminant hepatic failure because of the high prevalence of the disease.
Hepatitis C rarely causes acute liver failure. Hepatitis D, as a coinfection or
superinfection with hepatitis B virus, can lead to fulminant hepatic failure. Hepatitis E (often
observed in pregnant women) in endemic areas is an important cause of fulminant hepatic
failure.
Atypical causes of viral hepatitis and fulminant hepatic failure include the following:
 Cytomegalovirus
 Hemorrhagic fever viruses
 Herpes simplex virus
 Paramyxovirus
 Epstein-Barr virus
4. Toxins
 Amanita phalloides mushroom toxin
The amatoxins inhibit the hepatic formation of mRNA by binding to RNA
polymerase. Hepatocellular uptake of α-AMA, the major amatoxin, is followed by
significant hepatocyte damage and causes acute liver failure (ALF) in Amanita
phalloides intoxications. As a result of hepatocyte damage in the poisonings with
Amanita species, AST and ALT levels increase in the serum.
 Carbon tetrachloride
Carbon tetrachloride is another toxin that can cause acute liver failure. It is an
industrial chemical found in refrigerants and solvents for waxes, varnishes, and
other materials.
5. Malignancy- lymphoma, malignant infiltration

Fulminant liver failure may be seen as a terminal event in a patient already known
to have primary or secondary hepatic malignancy. Cancer that either begins in or
spreads to your liver can cause your liver to fail.
6. Vascular
 Budd-Chiari syndrome
Budd-Chiari syndrome is a condition in which the hepatic veins (veins that drain
the liver) are blocked or narrowed by a clot (mass of blood cells). This blockage
causes blood to back up into the liver, and as a result, the liver grows larger.

 Ischaemic injury
Ischemic hepatitis (also referred to as shock liver) refers to diffuse hepatic injury
resulting from acute hypoperfusion.
7. Miscellaneous
 Wilson’s disease
Wilson's disease is a rare inherited disorder that causes copper to accumulate in
your liver, brain, and other vital organs. Copper plays a key role in the development of
healthy nerves, bones, collagen, and the skin pigment melanin. Normally, copper is
absorbed from your food, and excess is excreted through a substance produced in your
liver (bile). But in people with Wilson's disease, copper isn't eliminated properly and
instead accumulates, possibly to a life-threatening level.
 Autoimmune hepatitis
Autoimmune hepatitis is liver inflammation that occurs when your body's
immune system turns against liver cells. The exact cause of autoimmune hepatitis is
unclear, but genetic and environmental factors appear to interact over time in triggering
the disease. Untreated autoimmune hepatitis can lead to scarring of the liver (cirrhosis)
and eventually to liver failure.
 Acute fatty liver of pregnancy

 HELLP syndrome
Acute fatty liver of pregnancy (AFLP) frequently culminates in fulminant

hepatic failure. AFLP typically occurs in the third trimester; preeclampsia develops in
approximately 50% of these patients. AFLP has been estimated to occur in 0.008% of
pregnancies. The most common cause of acute jaundice in pregnancy is acute viral
hepatitis, and most of these patients do not develop fulminant hepatic failure. The one
major exception to this is the pregnant patient who develops hepatitis E virus infection,
in whom progression to fulminant hepatic failure is unfortunately common and often
fatal.
The HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome occurs
in 0.1-0.6% of pregnancies. It is usually associated with preeclampsia and may rarely
result in liver failure.
Page 4 of 5
III. MANIFESTATIONS
 Increased Liver enzymes
 Right Upper Quadrant pain
 Hepatic encephalopathy
 Increased INR
 Increased serum bilirubin
 Jaundice
IV. TREATMENT
1. Manage in ICU at transplant center
2. Intravenous fluids to maintain blood pressure.
3. NAC (N- Acetylcysteine) administration (IV/PO)
4. Medications such as laxatives or enemas to flush toxins out.
5. Acyclovir until HSV/VZV is ruled out.
6. Blood transfusion for excessive bleeding.
7. Liver transplant.
V. Complications
1. Cerebral edema and Intracranial hypertension
2. Hypoglycemia
3. Increased risk of bleeding and clotting
4. Increased risk of infection

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NORTHWESTERN UNIVERSITY,INC

Laoag City, Ilocos Norte

ACUTE LIVER FAILURE

Acute liver failure (ALF) is an uncommon condition in which rapid deterioration of

Grade I Changes in behaviour, mild confusion, slurred speech, disordered

NCM 118: Responses to Metabolic- Gastrointestinal and Liver Alteration

 Antidepressants (amitriptyline, nortriptyline)

NCM 118: Responses to Metabolic- Gastrointestinal and Liver Alteration

3. Viral Hepatitis and other viruses

5. Malignancy- lymphoma, malignant infiltration

NCM 118: Responses to Metabolic- Gastrointestinal and Liver Alteration

 Acute fatty liver of pregnancy

Acute fatty liver of pregnancy (AFLP) frequently culminates in fulminant

NCM 118: Responses to Metabolic- Gastrointestinal and Liver Alteration

NCM 118: Responses to Metabolic- Gastrointestinal and Liver Alteration

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