Liver Failure

Liver (hepatic) failure is a loss of liver function because of the death of many hepatocytes. The damage can occur suddenly, as with a viral infection, or slowly over time, as with cirrhosis. Acute liver failure (ALF) refers to both fulminant hepatic failure (FHF) and subfulminant hepatic failure. FHF occurs when sudden (within 8 weeks from onset) severe liver decompensation caused by massive necrosis of the liver leads to coagulopathies and encephalopathy. Approximately 2,000 people in the United States develop FHF each year. Subfulminant hepatic failure, also known as late-onset hepatic failure, can take up to 26 weeks before hepatic encephalopathy develops. Hepatic encephalopathy occurs with neurological changes such as personality changes, changes in cognition and intellect, and reduced level of consciousness.

Because of the complex functions of the liver, liver failure leads to multiple system complications. When ammonia and other metabolic by-products are not metabolized, they accumulate in the blood and cause neurological deterioration. Cerebral edema likely results from impaired regulation of osmosis, resulting in swelling of brain cells and accumulation of toxic products of metabolism, particularly glutamine. Without normal vitamin K activation and the production of clotting factors, the patient has coagulation problems. Patients are at risk for infections because of general malnutrition, debilitation, impairment of phagocytosis, and decreased liver production of immune-related proteins. Fluid retention occurs because of decreased albumin production, leading to decreased colloidal osmotic pressure with failure to retain fluid in the bloodstream. Renin and aldosterone production cause sodium and water retention. Ascites occurs because of intrahepatic vascular obstruction with fluid movement into the peritoneum.

Complications of liver failure include bleeding esophageal varices (Box 1), hemorrhagic shock, hepatic encephalopathy, seizures, hepatorenal syndrome, coma, and even death.

Box 1 Bleeding Esophageal Varices

Esophageal varices (fragile, distended, and thin-walled veins in the esophagus) occur in patients with liver failure because of portal hypertension. Obstructed blood circulates to low-resistance alternate vessels around the portal circulation in the liver, which is a high-pressure system. One of these routes is through the esophageal veins, which become distended with blood, irritated from pressure, and susceptible to rupture. Treatment of esophageal varices includes the following:
Surgery. Procedures include placing a portal caval shunt or distal splenorenal shunt, esophageal repair, or devascularization.
Endoscopic Sclerotherapy. To cause fibrosis of the varices, patients are injected with solutions during an endoscopy procedure. Sodium tetradecyl sulfate or sodium morrhuate are commonly used sclerosants in the United States.
Esophageal Balloon Tamponade. Endoscopic therapy has replaced balloon tamponade in almost all situations. If balloon therapy is used, it is essential that it is initiated by an experienced clinician. In balloon tamponade, a multilumen gastrointestinal tube with an esophageal and gastric balloon is passed into the upper gastrointestinal tract through the patient's mouth. The gastric balloon, which is filled with 250 to 300 mL of air, acts as an anchor; the esophageal balloon, which is filled with enough air to cause 20 to 75 mm Hg pressure, compresses the esophageal varices to decrease bleeding. Traction may be inserted by taping the outer portions of the multilumen tube to the face mask of a football helmet.
Parenteral Therapy. Maintain a large-bore IV line and keep several units of packed cells on call from the blood bank at all times.
Vasopressin (Pitressin) Therapy. A continuous infusion of this vasoconstrictor causes constriction of the mesenteric circulation and decreased blood flow to the portal circulation.

Causes ⬆ ⬇

The leading causes of FHF are viral hepatitis and hepatotoxic drug reactions. The most common drug associated with liver failure is acetaminophen (42%), but idiosyncratic drug reactions (12%) also can lead to ALF. Although viral hepatitis can lead to liver failure, fewer than 5% of patients with viral hepatitis actually develop it. Other causes include chronic alcohol abuse, acute infection or hemorrhage that leads to shock, fatty liver of pregnancy, prolonged cholestasis (arrest of bile excretion), and metabolic disorders. Many of these lead to cirrhosis, a chronic liver disease that results in widespread tissue fibrosis, nodule formation, and necrosis of the liver tissue. Risk factors for liver failure include chronic alcohol abuse, poor nutrition, pregnancy, chronic hepatitis B and C, use of untested alternative/complementary medications, and narcotic abuse.

Genetic Considerations ⬆ ⬇

Autosomal dominant polycystic kidney disease is mainly caused by mutations in two genes (PKD1 and PKD2) that also increase susceptibility to liver cysts. Isolated liver cysts (the polycystic liver disease) have been linked to multiple genes (PRKCSH, SEC63, LRP5, and ALG8). Some affected persons develop massive hepatic cystic disease that results in liver failure. Wilson disease is an autosomal recessive genetic disorder caused by mutations in ATP7B, leading to a large liver accumulation of copper. About 5% of patients with Wilson disease suffer from acute liver failure or fulminant hepatitis.

Sex and Life Span Considerations ⬆ ⬇

Although acute liver failure can occur at any age, infants and children are more likely to have an inherited disease, whereas adult men are more likely to have alcohol-related disease. The poorest outcomes and mortality rates are found in children under 10 years or adults older than 40 years. Cirrhosis is the 12th leading cause of death in the United States and occurs most commonly between the ages of 35 and 55 years. Women develop acute liver failure at a later age than men and are more likely than men to have failure related to viral hepatitis E or autoimmune liver disease. Women are also more severely affected by alcohol- and drug-induced liver injury than men. Women are more likely to die while waiting for a liver transplant as compared to men.

Health Disparities and Sexual/Gender Minority Health ⬆ ⬇

White persons have the highest rates of ALF (74%), followed by Hispanic (10%), Asian (5%), and Black (3%) persons. Sexual and gender minority people have higher rates of alcohol consumption than the general population (Centers for Disease Control and Prevention, 2021), which may place them at risk for liver failure.

Global Health Considerations ⬆ ⬇

The cause of liver failure varies across different countries. Worldwide statistics indicate that postnecrotic cirrhosis is more common in women than men and is the most common type of liver failure worldwide. Acetaminophen overdose is a common cause of liver failure in Western Europe, whereas hepatitis B and hepatitis D viral infections are a major cause in developing countries. Hepatitis E virus is associated with liver failure in pregnant persons, particularly those living or traveling in developing regions in Mexico, India, China, and Northern Africa.

Assessment ⬆ ⬇

ASSESSMENT

History

Determine the patient's family history for liver disease. Take a detailed medication history with particular attention to hepatotoxic medications, such as anesthesia agents, analgesics, antiseizure medications, cocaine, alcohol, isoniazid, herbal medications, and oral contraceptives. Ask about any recent travel to China, southeast Asia, sub-Saharan Africa, the Pacific Islands, and areas around the Amazon River, which may have exposed the patient to hepatitis B. Explore the patient's occupational history for hepatitis exposure; patients who are day-care workers, dental workers, physicians, nurses, or hospital laboratory workers are particularly at risk. Ask if the patient has experienced previous liver or biliary disease. Elicit a history of IV drug use and/or men having sex with men, because these activities expose people to the risk for hepatitis and therefore liver failure. Those who eat raw shellfish are at similar risk.

Patients or families may describe early symptoms such as personality changes (agitation, forgetfulness, disorientation), fatigue, anorexia, drowsiness, and mild tremors. Some patients experience sleep disturbance and low-grade fevers. As larger areas of the liver are destroyed, patients have increasing fatigue, confusion, and lethargy. If patients have longstanding liver failure, they experience jaundice, dry skin, early morning nausea, vomiting, anorexia, weight loss, altered bowel habits, and epigastric discomfort. If sudden FHF occurs, patients may develop encephalopathy (decreased mental status, fixed facial expression), peripheral swelling, ascites, and bleeding tendencies. Urine is often dark from bilirubin, and stools are often light colored because of the absence of bilirubin.

Physical Examination

The patient with acute liver failure usually hasjaundiced skin and sclera. Fluid retention results in ascites and peripheral edema. The patient's facial expression appears fixed, movements are hesitant, and speech is slow. Usually, the patient's mental status is markedly decreased, and you may smell fetor hepaticus, a sweet fecal odor, on the patient's breath. The patient may have multiple bruises, a bloody nose, or bleeding gums.

The patient's peripheral pulses are bounding and rapid, indicating fluid overload and a hyperdynamic circulation. You may also palpate peripheral edema, an enlarged firm liver in acute failure and a small hard liver in chronic failure, an enlarged spleen, a distended abdomen, and an abdomen with shifting dullness to percussion and a positive fluid wave because of ascites. As ascites worsens, the patient develops hernias, an everted umbilicus, and an elevated and displaced heart because of a raised diaphragm. Usually, the patient with late disease has neck vein distention, and men develop gynecomastia (enlarged breasts), testicular atrophy, and scant body hair. When you monitor the patient's vital signs, you may find an elevated temperature and a low-to-normal blood pressure; if the physician initiates hemodynamic monitoring, the cardiac output may be low if ascites is decreasing the right ventricular filling pressure and if the systemic vascular resistance is low.

Psychosocial

The patient may feel upset or guilty if the patient contracted the disease while traveling. Use a nonjudgmental approach to elicit the patient's feelings if the condition is related to alcohol or drug abuse. If the patient is a candidate for a liver transplant, determine the patient's emotional stability, ability to cope with a complex medical regimen, and ability to rely on significant others.

Diagnostic Highlights

Test	Normal Result	Abnormality With Condition	Explanation
Prothrombin time	Varies by laboratory; generally 10–13 sec	Prolonged > 15 sec	Prothrombin is formed in the liver and is a vitamin K–dependent glycoprotein necessary for firm clot formation
Viral hepatitis seriologies: Hepatitis A virus (HAV); hepatitis B virus (HBV); hepatitis C virus (HCV); hepatitis D virus (HDV); hepatitis E virus (HEV) (see Hepatitis)	Negative results	If patient has hepatitis: acute HAV: positive anti-HAV IgM; acute HBV: anti-HBV IgM; HB surface antigen; acute HCV: anti-HCV antibody, HCV RNA; HDV: anti-HDV IgM, HDV antigen; HEV: not available; non-A, non-B: all tests negative	Identify patients with hepatitis; virus leads to markers such as immunoglobulins (IgG and IgM), antigens, antibodies
Liver function tests	Alanine aminotransferase (ALT): 19–36 units/L; aspartate aminotransferase (AST): 15–40 units/L; alkaline phosphatase: 25–142 units/L	ALT elevated as high as or higher than 1,000 units/L; AST elevated as high as or higher than 1,000 units/L; alkaline phosphatase mildly elevated	Determine the extent of liver damage

Other Tests: The most important aspect of the diagnostic work-up is to determine the underlying cause of liver failure. Tests include liver ultrasound, computed tomography, magnetic resonance imaging, drug and alcohol screening, bilirubin, lactate dehydrogenase, complete blood count, serum glucose, serum lactate, serum sodium and potassium, ammonia, albumin, and liver biopsy.

Primary Nursing Diagnosis ⬆ ⬇

Diagnosis

DiagnosisExcess fluid volume related to water and sodium retention as evidenced by rapid and bounding peripheral pulses, ascites, and/or peripheral edema

Outcomes

OutcomesFluid balance; Electrolyte balance; Fluid overload severity; Hydration; Nutrition status; Knowledge: Disease process; Knowledge: Treatment regimen

Interventions

InterventionsFluid/electrolyte management; Fluid monitoring; Medication administration; Nutrition management

Planning and Implementation ⬆ ⬇

PLANNING AND IMPLEMENTATION

Collaborative

Liver transplantation is the definitive treatment for ALF. More than 17,000 people are waiting for liver transplantation in the United States, and approximately 6,000 transplants are done each year. A liver transplant is indicated for patients with irreversible progressive liver disease who have no alternatives to transplantation, have life-threatening complications, or have the inability to sustain a normal quality of life. Patients with ALF who meet specific criteria can increase their transplant waitlist priority ahead of patients with liver failure caused by chronic liver disease.

While waiting for transplantation, if indicated, patients are managed with supportive therapy depending on their symptoms. Maintenance of airway, breathing, and circulation is the highest priority. Fluid and electrolyte imbalances, malnutrition, ascites, respiratory failure, cerebral edema, and bleeding esophageal varices can all occur with liver failure. Unless the patient has clinically significant hyponatremia, the patient usually receives limited IV fluids and food that contains sodium because increased sodium intake makes peripheral edema and ascites worse. Patients with ascites are usually restricted to 500 mg of sodium per day. A paracentesis may be used to remove 4 to 6 L of fluid. If the ascites is refractory, surgical placement of a peritoneal-venous shunt may be needed. Hypokalemia usually needs to be corrected with IV replacements. If the patient has serious fluid imbalances, a pulmonary artery catheter may be inserted for hemodynamic monitoring. If problems occur with coagulation, the patient may receive fresh frozen plasma.

Encephalopathy and cerebral edema are managed with hospitalization. Patients need serial neurological assessments. They should be positioned with the head of their bed elevated, and they may have continuous intracranial pressure (ICP) monitoring instituted. Because ammonia levels are increased due to liver failure, and since accumulation of ammonia and glutamine increase ICP, medications such as lactulose may be administered to reduce ammonia levels. Increased ICP may be managed with osmotic diuretics and hyperventilation. Other strategies may be the administration of hypertonic saline and/or barbiturate agents.

If respiratory failure is present, the patient may need endotracheal intubation and mechanical ventilation with supplemental oxygen. To manage nutrition in patients without evidence of hepatic encephalopathy, a high-calorie, 80- to 100-g protein diet is prescribed to allow for cellular repair. Some patients may need enteral or total parenteral nutrition to maintain calorie and protein levels. Hepatorenal failure is treated by fluid restriction, maintenance of fluid and electrolyte balance, and withdrawal of nephrotoxic drugs. Renal dialysis is generally not used because it does not improve survival and can lead to additional complications.

Pharmacologic Highlights

Medication or Drug Class	Dosage	Description	Rationale
Histamine receptor (H₂) antagonists	Varies with drug	Famotidine, cimetidine	Decrease gastric secretion; used as prophylaxis for ulcers
Thiamine	100 mg qd for several days or longer, depending on nutritional deficiencies	Vitamin supplement	Reduces risk for neuropathies
Vitamin K	Up to 10 mg IV as needed	Vitamin supplement	Needed for prothrombin production

Other Drugs: Sedatives and acetaminophen are avoided because poor metabolism can precipitate encephalopathy. Aspirin is usually avoided because of the action on platelets, which can lead to increased bleeding. If ascites is present, diuretics, particularly aldosterone antagonists such as spironolactone (Aldactone), may be prescribed and, if ineffective, more potent loop diuretics may be added. Mannitol may be used as an osmotic diuretic to reduce cerebral edema. Barbiturates such as pentobarbital and thiopental may be used for intracranial hypertension. Silibinin is a derivative of silymarin, an active ingredient in herbal preparations that possesses antioxidant properties; its use may benefit liver disease management.

Independent

The most common problem for patients with liver failure is fluid volume excess. Measure the patient's abdominal girth at the same location daily and mark the location as a reference point for future measurements. Notify the physician if the girth increases by 2 inches in 24 hours. Provide the required fluid allotment over the three meals and at night. If the patient desires, reserve some fluids to be used as ice chips. Provide mouth care every 2 hours. Because areas of edema are likely to be fragile and prone to skin breakdown, provide skin care.

One of the most life-threatening complications of liver failure is airway compromise because of neurological or respiratory deterioration. Keep endotracheal intubation equipment and an oral airway at the bedside at all times. Elevate the head of the patient's bed to 30 degrees to ease respirations and support the patient's arms on pillows to decrease the work of breathing. It is essential to be at the bedside and to perform serial assessments of all critical systems. Space all activities and limit visitors as needed so that the patient gets adequate rest. To encourage rest, consider nonpharmacologic methods such as diversionary activities and relaxation techniques.

The patient may be anxious, depressed, angry, or emotionally labile. Allow the patient to verbalize anxieties and fears. If needed, refer the patient to a counselor. Evaluate thoroughly anyone who is a candidate for a liver transplant to ensure that they have the ability to cope with a complex situation. Answer all questions, and explain the risks and benefits. Refer to an alcohol counselor if appropriate.

Depending on the patient's condition, discussion of end-of-life care might be appropriate. Opening discussion of the patient's desires for hospice care may be appropriate, as may discussion about the patient's preferences for a funeral. The patient and family will need privacy for these discussions.

Evidence-Based Practice and Health Policy

Patterson, J., Hussey, H., Silal, S., Goddard, L., Setshedi, M., Spearman, W., Hussey, G., Kagina, B., & Muloiwa, R. (2020). Systematic review of the global epidemiology of viral-induced acute liver failure. BMJ Open. Advance online publication. http://doi.org/10.1136/bmjopen-2020-037473

The authors conducted a systematic review to explain the epidemiology of viral-induced ALF to facilitate clinical case management and case prevention. They searched electronic databases and located 25 eligible studies. They estimated the burden of ALF after infection with HBV, HAV, HCV, HEV, herpes simplex virus/human herpesvirus, cytomegalovirus, Epstein-Barr virus, and parvovirus B19.
The prevalence of hepatitis A–induced ALF was markedly lower in countries with routine hepatitis A immunization versus no routine hepatitis A immunization. HEV was the most common cause of viral-induced ALF. Viral-induced ALF had poor outcomes as indicated by high fatality rates, which appear to increase with poor economic status of the studied countries.

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DRG Information ⬇

Introduction ⬆ ⬇