Many nurses view LFTs as one of the most difficult sets of laboratory tests to interpret. A complex organ, the liver manufactures, stores, alters, and excretes many substances involved in metabolism. The entire body is affected by disease or malfunction of the liver. It’s essential that nurses be informed about LFTs, the implications related to patients’ health, and the nursing considerations for care.

Anatomy and physiology of the liver

An understanding of the anatomy and physiology of the liver is essential to interpret LFTs accurately. The liver is located in the right upper quadrant of the abdomen. It extends from the fifth intercostal space in the midclavicular line to the right costal margin. During respiratory inspiration, the lower margin of the liver descends below the costal margin. The liver is composed of four lobes, each surrounded by connective tissue that extends into the lobe itself, dividing the liver mass into smaller units called lobules.¹

There are two sources of hepatic blood flow. The first is the portal vein, which supplies 75% of the blood to the liver. The nutrient-rich portal vein drains the gastrointestinal tract. The second source is the oxygen-rich hepatic artery, which supplies the remaining 25% of blood flow. These two vessels converge to form capillary beds. Liver cells, also known as hepatocytes, are bathed in this mixture of venous and arterial blood. Blood exits the liver through the central veins located in the center of each liver lobule. Central veins merge to form the hepatic vein, which empties into the inferior vena cava. In addition to hepatocytes, the liver is also composed of Kupffer’s cells. Kupffer’s cells are phagocytic and engulf bacteria and other invading particles that enter the liver through the portal vein.¹

Small bile ducts between the lobules of the liver are known as canaliculi. Canaliculi receive secretions from the hepatocytes and carry them to larger bile ducts, which form the hepatic duct. The hepatic duct and the cystic duct from the gallbladder converge to form the common bile duct. The common bile duct enters the duodenum at Oddi’s sphincter, which controls the flow of bile into the intestine.¹ 

Liver function

Functions of the liver include glucose, protein, and fat metabolism; ammonia conversion; vitamin and iron storage; drug metabolism; bile formation; and bilirubin excretion.¹

Glucose metabolism: The liver controls glucose metabolism and regulation of serum glucose. After eating, the liver takes glucose from the portal venous blood and converts it to glycogen. Glycogen is stored in the hepatocytes and is subsequently converted back into glucose. Glucose is released as needed into the bloodstream to maintain normal levels of blood glucose.¹

Protein metabolism: The liver synthesizes all plasma proteins such as albumin, alpha and beta globulins, blood-clotting factors, specific transport proteins, and most plasma lipoproteins. Amino acids are the building blocks for protein synthesis.¹ 

Fat metabolism: Fatty acids are broken down for the production of energy and ketones. Ketones enter the bloodstream and provide a source of energy for muscles and other tissues. Ketones are primarily produced when the glucose supply is limited, such as in starvation or uncontrolled diabetes. Fatty acids are also used for the synthesis of cholesterol, lipoproteins, and other complex lipids.¹

Ammonia conversion: Ammonia, a toxin, is produced by bacteria in the intestine. The liver converts this ammonia to urea, a nontoxic substance. Urea is safely excreted in the urine.¹

Vitamin and iron storage: Vitamins A, B, and D and several B-complex vitamins are stored in large amounts in the liver. Iron and copper are also stored in the liver.¹

Drug metabolism: The liver and the kidney are the two major organs responsible for eliminating drugs from the body. Both organs share metabolic and excretory functions. The liver is principally responsible for metabolism, and the kidneys control elimination. The physical and chemical properties of a drug are important in determining drug disposition. For example, lipophilic drugs tend to be distributed through the body and metabolized in the liver. Hydrophilic drugs have limited distribution and are rapidly eliminated by the kidneys.¹ 

Drugs undergo biotransformation — also known as metabolism — and/or excretion. Metabolism involves the conversion of the drug into another substance. Usually, metabolism results in the formation of an inactive substance, a metabolite, which is then eliminated from the body faster than the parent drug. While the major organ for biotransformation is the liver, the intestines, kidneys, and lungs also metabolize some drugs. Many drug metabolites are pharmacologically active and may have effects that are similar to or different from the parent molecule. However, they may also be responsible for toxic effects after administration. Drug metabolites may also serve as the desired active drug resulting from the metabolism of an inactive prodrug.¹

Bile formation: Bile is mainly composed of water and electrolytes such as potassium, sodium, calcium, chloride, and bicarbonate. It also contains significant amounts of lecithin, fatty acids, cholesterol, bilirubin, and bile salts. Bile is formed by the hepatocytes, collects in the canaliculi and bile ducts, and is stored in the gallbladder. Bile serves as an aid to digestion by emulsifying fats and excreting bilirubin.¹

Bilirubin excretion: Bilirubin is a pigment derived from the breakdown of hemoglobin. Hepatocytes remove bilirubin from the blood and modify it chemically through conjugation with glucuronic acid, which makes the bilirubin more water soluble. The conjugated bilirubin is secreted by hepatocytes in the bile canaliculi and is carried in the bile to the duodenum.¹

In the small intestine, bilirubin is converted into urobilinogen. Some urobilinogen is then excreted in the feces, while the rest is absorbed through the intestine into the portal blood. This reabsorbed urobilinogen is removed by the hepatocytes and is secreted into the bile once again. This enterohepatic circulation is the major excretory route of bilirubin. Some urobilinogen enters systemic circulation and is excreted in the urine.^{1, 2}

Physical examination

Physical signs may occur with liver damage. Disruptions of bilirubin metabolism and bile formation contribute to skin pallor, jaundice, muscle atrophy, skin excoriation from scratching, petechiae, ecchymosis, spider angiomas, and palmar erythema. The male patient is examined for gynecomastia and testicular atrophy resulting from endocrine changes. Observe and examine the patient’s cognitive status including recall, memory, and abstract thinking. The patient’s neurological status should be assessed for tremor, asterixis, weakness, and slurred speech. Cognitive and neurologic changes may be related to metabolic liver dysfunction or elevated ammonia levels that contribute to hepatic encephalopathy.¹ It is important for the nurse to monitor for these signs. Early intervention and management may decrease the extent of liver damage.

The abdominal exam is of extreme importance in the patient with liver damage. Assess for dilated abdominal wall veins and ascites. Test for ascites — or the presence of a fluid wave — by having the patient or another examiner place his hand firmly on the abdomen midline. The examiner’s left hand is placed on the patient’s right flank. The examiner uses his right hand to give the left flank a firm tap. The presence of ascites generates a fluid wave that the examiner will feel as a tap on his left hand. The liver is palpated by placing the examiner’s left hand under the patient’s back, parallel to the 11th and 12th ribs, and lifting upward to support the abdominal contents. The examiner’s right hand is placed on the patient’s right upper quadrant with fingers parallel to the midline as the patient takes a deep breath. It’s normal to feel the firm ridge of the lower aspect of the liver bump the examiner’s fingers as the liver is pushed downward with inspiration. However, the liver may not be palpable, and this is also a normal finding. If the liver is enlarged, it may be palpated more than 1 cm to 2 cm below the right costal margin. Document the number of centimeters the liver descends, its consistency, and any tenderness.¹

The liver panel

More than 70% of the liver parenchyma may be damaged before LFTs become abnormal.¹ LFTs are measures of serum enzyme activity and serum concentrations of proteins, bilirubin, ammonia, clotting factors, and lipids. The term liver panel is used to describe a group of tests ordered collectively to assess the liver. The liver panel may differ from institution to institution. Common components of the liver panel include: AST (aspartate aminotransferase), ALT (alanine aminotransferase), bilirubin, total protein, albumin, and ALP (alkaline phosphatase). A GGT (gamma-glutamyl transpeptidase) is not always included in the liver panel, but is an important test of liver function. Of note, the liver tests AST and ALT are formerly known as SGOT (serum glutamic-oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase), respectively. Refer to Table 1 for normal values for each liver function test. Normal laboratory values vary from one institution to the next.²

Indications for liver panel assessment

The indications for liver panel assessment are varied and stem from the patient’s complete health history and physical assessment. More specifically, liver function testing is warranted when the patient is exposed to hepatotoxic substances or infectious agents (occupational, recreational, and travel), has a history of alcohol or IV drug abuse, or has a medication history of drugs known to affect hepatic function. Medications known to affect hepatic function are numerous. Examples include acetaminophen (Tylenol), HMG-CoA inhibitors (also known as statin drugs), ketoconazole (Nizoral), valproic acid (Depakote), herbal remedies, and vitamins. Hepatotoxic herbs include peppermint, mistletoe, yerba tea, sassafras, germander, chaparral, skull cap, nutmeg, valerian, jin bu juan, comfrey (bush tea), pennyroyal, and tansy ragwortsenna. Iron supplements are not recommended unless otherwise noted by a physician.²

The patient’s family history can also provide insight into genetic diseases that affect the liver, such as alcohol abuse and hemochromatosis, a condition in which the small intestine absorbs excessive iron . Symptoms that may indicate the need for liver function testing include jaundice, malaise, weakness, fatigue, pruritus, abdominal pain, fever, anorexia, weight gain, edema, increased abdominal girth, hematemesis, melena, hematochezia, easy bruising, decreased libido in men, secondary amenorrhea in women, personality changes, and sleep disturbances.¹

Liver panel components

There are several components to the liver panel. Each component relays information regarding a patient’s physiological status. Proper interpretation of each component guides nursing care and ensures optimal results for the patient.

Aspartate aminotransferase (AST): AST is an intracellular enzyme involved in amino acid and carbohydrate metabolism. Hepatocytes lyse when disease or injury affect liver tissue. Lysis of the hepatocytes results in the release of AST into the bloodstream, increasing serum levels of AST. The amount of AST elevation is proportional to the extent of the injury or the number of affected cells. In addition, serum AST elevation depends upon the lapse of time between the injury and the time of venipuncture. Serum AST levels rise eight hours after injury, peak at 24 to 36 hours, and return to normal within three to seven days. Therefore, AST elevations from an acute tissue injury may clear in a few days. Chronic cellular injury results in persistently elevated serum levels of AST.^2,3

Interpreting results: AST is also present in other organs with high metabolic activity. It’s found in (decreasing order of concentration) the liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas, lungs, leukocytes, and erythrocytes.⁴ In fact, the AST measurement was once used in the evaluation of acute myocardial infarction (MI). However, AST measurement has been replaced with newer, more cardiac-specific tests to evaluate for MI. Since AST is present in organs with high metabolic activity, it’s not specific to the liver. Therefore, in patients with elevated AST and suspected liver disease, confirm that the ALT is also elevated. If the ALT is normal, a muscle source is likely.⁵

Acute hepatitis can cause AST levels to rise to 20 times the normal value. AST levels quickly rise up to 10 times the normal level and fall suddenly in patients with extrahepatic dysfunction (cholecystitis). The level of AST elevation beyond the norm depends on the amount of active inflammation in patients with cirrhosis . It’s important to remember that AST is not specific to the liver; therefore, transient increases in the level may be attributed to acute pancreatitis, musculoskeletal diseases, acute renal disease, or trauma. Red blood cell abnormalities can also cause an elevated AST level in patients with hemolytic anemia and burns.²

Liver diseases associated with elevated AST levels include: hepatitis, hepatic cirrhosis, drug-induced liver injury, hepatic metastasis, hepatic necrosis in the initial stages only, hepatic surgery, infectious mononucleosis with hepatitis, and hepatic tumor. Diseases and conditions associated with decreased levels of AST include: acute renal disease, beriberi (a condition caused by a lack of thiamine), diabetic ketoacidosis, pregnancy, and chronic renal dialysis.²

IM injections are known to increase AST levels because of tissue injury from needle insertion. Avoid IM injections near the time of the venipuncture. Be sure to record all injections so that increased levels of AST can be analyzed with this information in mind. If possible, and if ordered by the healthcare provider, hold drugs that may interfere with test results for 12 hours before the liver function test. Indicate on the laboratory slip any drugs that may interfere with the test. As with any lab test, record the exact date and time the venipuncture is performed in the medical record and include this information on the specimen vial.²

Alanine aminotransferase (ALT): ALT is an intracellular enzyme found predominantly in the liver and is involved in amino acid and carbohydrate metabolism . Liver injury or disease causes a release of ALT into the bloodstream, resulting in elevated ALT serum levels. Most ALT elevations are caused by liver disease. This enzyme is both sensitive and specific in indicating hepatocellular disease. ALT is commonly used as part of the differential diagnosis of liver disease.^2,3

Interpreting results: ALT levels may be used to monitor the course of hepatitis or cirrhosis or the effects of treatments that may be toxic to the liver. More commonly, the ALT level is used in a ratio with the AST level to provide valuable diagnostic information. The AST/ALT ratio is usually greater than 1.0 u/L in patients with alcoholic cirrhosis, liver congestion, and liver metastasis.^2,4 Patients with acute hepatitis, viral hepatitis, or infectious mononucleosis may have a ratio less than 1.0 u/L.2 The ratio is less accurate if AST levels exceed 10 times their normal value.

As with AST, IM injections may cause transient increases in ALT levels. No fasting is required before venipuncture. Because patients with liver disease can have prolonged bleeding time, apply pressure to the venipuncture site as long as necessary after drawing blood.²

Bilirubin: Bilirubin is the orange-colored or yellowish pigment in bile. At the end of the red blood cells’ 120-day life cycle, RBC degradation initiates bilirubin metabolism. More specifically, hemoglobin breaks down into heme and globin molecules. Heme is converted to biliverdin, which is ultimately transformed into bilirubin. This form of bilirubin is unconjugated, or indirect bilirubin. Indirect bilirubin is present in the blood and is fat soluble. More than 90% of bilirubin in people without liver dysfunction is in the unconjugated form.⁶

Indirect bilirubin is combined with a glucuronide, resulting in the conjugated, or direct, form of bilirubin. This direct bilirubin is then excreted from the hepatocytes and into the intrahepatic canaliculi, which lead to the hepatic ducts, common bile ducts, and eventually the bowel.

Direct bilirubin is either excreted unchanged in the stool or metabolized by ileal and colonic bacteria to urobilinogen. Urobilinogen can be reabsorbed in the small intestine and colon and enters portal circulation. Some urobilinogen is taken up by the liver and re-excreted into bile. The remainder bypasses the liver and is excreted by the kidney. Direct bilirubin is water soluble and thus able to be filtered by the renal glomeruli in the kidneys and excreted in the urine.¹ 

Abnormally high bilirubin levels cause jaundice. Jaundice is a yellow or yellow-green discoloration of the skin and body tissues, such as the sclera of the eye, which can be recognized when the bilirubin level exceeds 2.5 mg/dL.² Newborns with immature livers do not have enough conjugating enzymes. As such, the excess unconjugated bilirubin circulates in the bloodstream, increasing serum levels of bilirubin. Excess bilirubin is deposited in the tissues and passes through the blood-brain barrier into the brain cells. This can cause encephalopathy, also known as kernicterus. 

The primary concern when interpreting bilirubin results, whether noticed clinically or chemically, is whether the origin of the abnormality is predominantly caused by unconjugated indirect bilirubin or conjugated direct bilirubin. Understanding the origin of the defect helps determine therapeutic options.

The total serum bilirubin level is the sum of the conjugated and unconjugated bilirubin. Usually, the unconjugated bilirubin makes up 70% to 85% of the total bilirubin. When more than 50% of the bilirubin is conjugated in jaundiced patients, it is considered a conjugated hyperbilirubinemia. Conjugated hyperbilirubinemia is generally caused by extrahepatic obstruction of the bile ducts, as in gallstones, tumors, inflammation, or scarring. Unconjugated hyperbilirubinemia exists when less than 15% to 20% of the total bilirubin is conjugated. This type of jaundice is caused by hepatocellular dysfunction, as in hepatitis or accelerated RBC hemolysis.²

Fasting requirements vary for testing bilirubin levels. Some laboratories require that the patient have nothing by mouth except for water after midnight the day of the test. Blood hemolysis and lipemia can cause erroneous results. In addition, the blood tube must not be shaken and must be protected from bright light (sunlight or artificial lights). Exposure to light longer than 60 minutes can reduce bilirubin content. Lastly, pressure must be applied to the venipuncture site, as jaundiced patients may have prolonged bleeding times.²

Protein and albumin: Protein is found in muscle, enzymes, hormones, hemoglobin, and other important structures of the body. Proteins contribute to maintaining osmotic pressure within the vascular space, thus preventing fluid movement into surrounding tissue.¹

Albumin and globulin constitute most of the protein in the body and are measured in the total protein lab value. Albumin is an important measure of hepatic function. It is synthesized in the liver and comprises approximately 60% of the total protein level.  Various albumin functions include the maintenance of osmotic pressure and the transport of drugs, hormones, and enzymes. When the liver is diseased, hepatocytes lose the ability to produce albumin. Thus, the serum albumin level may be significantly decreased.² 

Globulins make up approximately 38% of all plasma proteins and control osmotic pressure to a lesser degree than albumin. Globulins participate in the immune response as the building blocks of antibodies and are also involved in the transport of blood substances.³

Serum albumin and globulin are measures of nutrition. Increased albumin levels may be an indication of dehydration. Decreased albumin levels may indicate malnutrition, pregnancy, liver disease, protein-losing nephropathy, third-space losses, overhydration, and inflammatory disease. Increased globulin levels may be related to inflammatory diseases, nephritic syndrome, hyperlipidemia, and iron deficiency anemia. Decreased globulin levels may be an indication of hemolysis, Wilson’s disease (a disorder associated with increased absorption of copper), hyperthyroidism, severe liver dysfunction, or malnutrition.²

No fasting is required before protein testing. As with any liver function test, 5 ml to 7 ml of blood are collected in a red-top or serum separator tube. Prolonged application of a tourniquet may increase protein levels. Sampling peripheral venous blood proximal to an IV site may result in false low protein levels.²

Alkaline phosphatase (ALP): The highest concentration of ALP is found in the liver and bone. However, it is also found in the intestine, kidney, and placenta. In the liver, ALP is an enzyme found on the canalicular surface, making it useful as a test for liver dysfunction. ALP is present in the Kupffer’s cells and is excreted into the bile.²

Because ALP is found in several places in the body and the serum ALP level is composed of isoenzymes from each source, separation of the sources is necessary. Electrophoresis separates the genetically distinct isoenzymes, allowing distinction to be made between liver and bone sources.² 

Levels of ALP are greatly increased in extrahepatic and intrahepatic obstructive biliary disease and cirrhosis. Levels are mildly increased with hepatic tumors, hepatotoxic drugs, and hepatitis. The most sensitive test for metastatic tumor to the liver is ALP. In addition, new bone growth is associated with elevated ALP and may be a normal finding in the growing adolescent. However, elevated ALP levels can also indicate pathological sources, such as in breast and prostate tumors, Paget’s disease, healing fractures, rheumatoid arthritis, and hyperparathyroidism. Decreased ALP levels are associated with hypothyroidism, malnutrition, pernicious anemia, hypophosphatemia, scurvy, celiac disease, and excess vitamin B6 ingestion.²

Fasting is not usually required before venipuncture, although it may be required by some laboratories for isoenzyme testing. A recent meal may increase ALP levels.²

Gamma-glutamyl transpeptidase (GGT): GGT is an enzyme that regulates the transport of amino acids across cell membranes. High concentrations of GGT are found in the liver and biliary tract. This test is used to detect liver cell dysfunction and indicates even the slightest degree of cholestasis. GGT is the most sensitive liver enzyme for detecting biliary obstruction, cholangitis, or cholecystitis.² 

The major use of GGT is to discriminate the source of an elevated serum ALP level. For example, if the ALP is elevated and the GGT is also elevated, the source is most likely the biliary tract. Conversely, if the ALT is elevated and GGT is normal, the source is probably skeletal disease. GGT is also useful in detecting chronic alcohol ingestion, as it is elevated in approximately 75% of patients who chronically drink alcohol. GGT may also be elevated one to two weeks after an MI, for reasons that are not clear.²

Generally, an eight-hour fast is recommended before this test. Indicate on the laboratory slip any medications the patient is taking that may affect the GGT level.² 

Influence of drugs on liver function

Because many drugs are metabolized in the liver, there is potential for a great number of drugs to affect liver function . Table 2 shows the impact of several drugs on each liver function test.

The liver is responsible for many important body functions. Because homeostasis of the liver is paramount to proper body function, virtually every patient in the hospital undergoes live function tests. These tests find abnormalities that may result in illnesses including hepatitis, cirrhosis, hepatitic tumor, cholestasis, and pancreatitis. An understanding of the indications for liver function tests, normal and abnormal values, and impact on patient care are essential to help the nurse reduce morbidity and mortality and improve patients’ functional status.