Acute Liver Failure

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by V. J. , RN, BSN, MA

Article Date: 5/17/2004

Liver Failure is a condition that develops when a large portion of liver tissue is damaged as a result of exposure to infectious disease, toxic chemicals or drug overdose.

There are two types of acute liver failure:

Fulminant Hepatic Failure. Fulminant hepatic failure (FHF) is characterized by coagulopathy (bleeding disorders) and encephalopathy (mental impairment) that develop within 8 weeks of the onset of illness.

Subfulminant Hepatic Failure. Also known as late-onset hepatic failure, subfulminant hepatic failure occurs in people with chronic liver disease; that is, those people who have had some form of liver disease for at least 6 months prior to the development of encephalopathy.

What causes Acute Liver Failure?

Acetaminophen. As acetaminophen is metabolized by the liver, a toxic metabolite is produced that promotes liver damage by contributing to the formation of oxygen free radicals, substances capable of damaging liver tissue. Usually, the presence of antioxidants in the liver, specifically a substance called glutathione, is able to neutralize the effect of oxygen free radicals and prevent damage to liver tissue, but this defense mechanism can sometimes be inadequate.

In the event of accidental or intentional overdose of acetaminophen, the volume of oxygen free radicals produced as the drug is metabolized simply exceeds the reserves of antioxidant substances, inducing a state of oxidative stress, and leading to the direct destruction of liver tissue.

However, an overdose of acetaminophen is not always necessary to produce toxicity. People who consume alcohol regularly (but are not necessarily alcohol abusers or alcoholics) can steadily deplete reserves of glutathione in the liver.

In these cases, an otherwise safe dose of acetaminophen can produce a sufficient quantity of oxygen free radicals to overwhelm the depleted antioxidant reserves, causing sufficient oxidative stress to initiate liver inflammation and cellular destruction.

Viral Hepatitis. Hepatitis A infection can lead to liver failure, and although this is uncommon, as many as 20% of the pediatric liver transplants in some countries are the result of HAV-induced fulminant hepatic failure.

In developing countries, hepatitis B (HBV) infection is a major cause of FHF and is complicated by hepatitis delta virus (HDV) superinfection. Hepatitis E virus (HEV) is generally a mild form of viral hepatitis similar to HAV, but can cause FHF in pregnant women.

Idiosyncratic Drug Reactions. Drug reactions are sometimes the cause of liver failure. Patients suffering from liver failure as a result of drug reactions tend to have lower aminotransferases (liver enzymes), but higher bilirubin levels and more frequent ascites (learn more about common liver laboratory tests). Fortunately, the progression of liver failure is slower in this group, and this increases the chances of the patient obtaining a liver transplant.

Drugs that have been associated with liver failure include:

Allopurinol (for Gout) Amiodarone (regulates heart activity) Chlorpromazine (antipsychotic, antianxiety) Chlorpropamide (antidiabetic) Disulfiram (alcohol use deterrent) Erythromycin estolate (antibiotic) Gold (antirheumatic) Halothane (inhalation anesthetic) Isofluorane (inhalation anesthetic) Enflurane (inhalation anesthetic) Isoniazid (antitubercular) Ketoconazole (antifungal) Methyldopa (antihypertensive) Monoamine oxidase inhibitors (antidepressant) Nitrofurantoin (antibiotic) Nonsteroidal anti-inflammatory drugs Phenytoin (anticonvulsant) Propylthiouracil (anti-hyperthyroid) Rifampicin (antimycobacterial ) Sulfonamides (antibiotic) Tetracycline (antibiotic) Valproic acid (anticonvulsant)

Other causes of acute liver failure include:

Illicit drugs, such as ecstasy and cocaine Certain herbal or alternative medicines, such as ginseng, pennyroyal oil, golden germander (Teucrium polium) and Chaparral or germander tea (learn more about herbs) Toxins, including the Death Cap mushroom (Amanita phalloides), bacillus cereus toxin, cyanobacteria toxin, organic solvents (e.g., carbon tetrachloride) and yellow phosphorus.

How is Acute Liver Failure diagnosed?

The patient with acute liver failure may demonstrate the following signs:

Encephalopathy: mental derangement ranging from confusion and disorientation to deep coma Jaundice: yellow discoloration of skin and eyes resutling form increased levels of serum bilirubin Fetor Hepaticus: a strong "bad breath" odor characteristic of liver disease Asterixis: a movement disturbance characterized by flapping tremors and jerky, irregular movements at the wrist Slurred speech Hepatomegaly: enlarged liver Skin lesions characteristic of liver disease, including spider veins Fluid balance disorders: Ascites (accumulation of fluid in the abdomen) and Anasarca (whole body edema)

Analysis of laboratory data can reveal:

Thrombocytopenia: decreased platelet counts Prolonged PT/INR: a decreased ability to form blood clots to stop bleeding Elevated Aminotransferases (ALT and AST): also known as liver enzymes, these substances are released into serum as liver cells are injured. They may be as high as 40 times the normal range Elevated Bilirubin: a byproduct of the breakdown of red blood cells that causes jaundice Elevated Ammonia: a toxic byproduct of protein metabolism, normally removed by the liver

Complications in Acute Liver Failure

There are several conditions that can develop during acute liver failure that suggest a poor prognosis.

Cerebral Edema. This condition results from disordered fluid balance, and causes an accumulation of fluid (edema) in the brain. This interferes with the normal functioning of the brain, and can contribute to the cognitive impairment caused by hepatic encephalopathy (contamination of the brain by toxic metabolic waste products).

Additionally, the brain may sustain direct injury as a result of edema; it is located within a confined space (the skull) and has little room to expand as the fluid volume in the skull increases.

Multiorgan failure. As liver function deteriorates, many of its regulatory and synthetic functions are markedly diminished. In particular, the vascular system may be affected, causing a sudden decrease in blood flow to other organs. Any sudden decrease in blood pressure can cause ischemia (low oxygen) in organ tissues, causing organs to sustain damage and lose some or all of their function.

Additionally, patients with severe liver damage may lose the ability to staunch bleeding (coagulopathy), so decreased organ oxygen perfusion may be a direct result of inadequate blood flow caused by internal or external bleeding.

Sepsis. Sepsis, the presence of disease-causing organisms in the blood, is a cause of mortality in acute liver failure. Sepsis can cause a profound drop in blood pressure resulting in organ ischemia, and contributing to multiorgan failure. A common cause of sepsis in patients with ascites (accumulation of fluid in the abdomen) is spontaneous bacterial peritonitis (SBP).

SBP is an infection and inflammation of the peritoneum, the membrane that lines the wall of the abdomen and covers the abdominal organs. It is caused by bacteria that may be part of the normal flora of the intestine. Respiratory Failure. As the patient progresses through increasingly severe stages of hepatic encephalopathy, the brain's ability to maintain adequate respiration may be compromised, requiring the implementation of mechanical ventilation.

Hemorrhage. The loss of the liver's ability to produce the substances necessary for blood clotting can result in massive bleeding. Bleeding in the gastrointestinal tract can result from esophageal or gastric varices, a common consequence of portal hypertension. Patients may require transfusions of large volumes of platelets and red blood cells.

Prognosis in Acute Liver Failure

The prognosis for a person with acute liver failure depends greatly on the cause of the illness, the development of complications, and the age of the patient.

In cases of acetaminophen toxicity, the following factors are associated with a poorer prognosis:

Coma Decreased arterial blood pH Increased Prothrombin time (PT), increasing the risk of severe bleeding Serum creatinine elevated higher than 300 mcg/mL (3.4 mg/dL)

Clinicians at King's College Hospital in London has developed a set of prognostic indicators for cases of FHF not due to acetaminophen toxicity, finding these factors to be associated with poorer outcomes:

Prothrombin time (PT) greater than 100 seconds, plus any 3 of the following:

Patient age younger than 10 years or older than 40 years FHF due to HDV, HEV, halothane inhalation for anesthesia, or idiosyncratic drug reactions Jaundice present more than 1 week before onset of encephalopathy Serum bilirubin greater than 300 mmol/L (17.5 mg/dL).

Not all cases of FHF require a liver transplant. FHF caused by acetaminophen, shock, hepatitis A, and pregnancy are least likely to require transplant for survival. However, the treatment for liver failure caused by other forms of viral hepatitis, idiosyncratic drug reactions and toxic exposure usually requires liver transplant.

What is the Treatment for Acute Liver Failure?

Certain medical interventions may be implemented to decrease toxicities, and manage complications. For example, acetaminophen toxicity is treated by administering a drug called n-acetyl-l-cysteine. However, the treatment of liver failure commonly involves liver transplant (learn more about liver transplant).

Sources

, B. Hepatic Failure. www.emedicine.com, 2004.

Alconzo, M. Acute Hepatic Failure. INTOX Project, International Programme on Chemical Safety. 1999. http://www.intox.org/

Lee, W. Acute Liver Failure in the United States. Semin Liver Dis 23(3):217-226, 2003.

Gomersall, C. Fulminant hepatic failure. The Chinese University of Hong Kong. 2004. http://www.aic.cuhk.edu.hk/web8/fulminant_hepatic_failure.htm V.J. is a Registered Nurse with a Bachelor's degree in Nursing and a Master's degree in Clinical Psychology, and has experience in oncology, critical care and hospice, nursing management, counseling and clinical administration.

Hepatitis A: What is it?

Hepatitis B: What is it?

Basic Information About Hepatitis C

Hepatitis D

Hepatitis E

Alcoholic Liver Disease

Cirrhosis of the Liver

End Stage Liver Disease

Liver CancerLiver Transplant

WHO: Fulminant Hepatic Failure in HBV

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