Description
- "Liver function tests" (LFTs) is the common vernacular for the standard biochemistry profile provided by most laboratories. It typically includes:
- LFTs are more accurately described as tests of overall liver health (metabolic and synthetic function) or inflammation (necrosis).
- True, specific tests of liver function (galactose clearance, aminopyrine clearance) are not widely used.
- Aspartate transaminase (also known as serum glutamic oxaloacetic transaminase [SGOT]) is an enzyme found in liver parenchymal cells, brain, heart, kidneys, muscle, and red blood cells. It is responsible for transferring the aspartate amino group to ketoglutaric acid. Elevated levels may indicate tissue damage or inflammation.
- Alanine aminotransferase (also known as serum glutamic pyruvic transaminase [SGPT]) is an enzyme found primarily in liver parenchymal cells and, to a lesser extent, in the heart, kidneys, and muscle. It is responsible for transferring the alanine amino group to ketoglutaric acid. Values provide a measure of hepatic damage or inflammation and are considered more specific than AST values.
- Alkaline phosphatase is an enzyme that catalyzes hydrolysis of phosphate esters at an alkaline pH. More than 80% is found in the liver and bone; minor sites include the placenta, intestine, and kidney. Measurements indicate inflammation, particularly in the biliary tract.
- Bilirubin is the byproduct of heme catabolism. When hemoglobin is released from red blood cells (normal breakdown, damaged or old cells), the globin is turned into amino acids. In reticuloendothelial cells, the heme is converted into unconjugated bilirubin which is water-insoluble and binds to albumin. The liver conjugates it with glucuronic acid to form conjugated bilirubin, which is water-soluble. Bilirubin values can, thus, provide a measure of hepatic metabolic function.
- Albumin is synthesized by the liver and comprises 60% of plasma proteins. It has a serum half-life of approximately 20 days. Measurements indicate hepatic synthetic function, but do not necessarily reflect acute processes. Normal adult values: 3.4–5.4 g/dL.
Physiology/Pathophysiology
- As many as 1/3rd of patients screened may have a nonspecific abnormality in LFTs. Incidence of clinically significant disease is ~1%.
- Differential diagnosis can be broken down into:
- Hepatocellular inflammation or dysfunction: Inflammation and necrosis of hepatocytes result in the release of AST and ALT (e.g., hepatitis A). Normal levels of AST and ALT do not fall within a Gaussian distribution. Instead, distribution is skewed rightward, meaning levels up to 1.5 the upper limits of "normal" do not necessarily suggest liver disease. Hepatic dysfunction results in decreased metabolic and/or synthetic function.
- Cholestatic disease: Includes intrahepatic and extrahepatic processes and is usually accompanied by an elevation in bilirubin (direct or indirect) and/or alkaline phosphatase.
- Infiltrative disease such as amyloidosis can result in the release of AST and ALT as well as decreased metabolic and synthetic function.
- Clinical history is important to help differentiate between causes:
- Family history is relevant since many genetic disorders can affect liver function (Gilbert's and Dubin Johnson, Wilson's disease, etc.).
- Sexual and social history, travel, and work exposure can also point to causes such as viral hepatitis.
- Systemic conditions affecting LFTs include cardiac disease, inflammatory bowel disease, diabetes, arthritis, hypogonadism, and thyroid disease.
- Transaminases:
- Since AST is less specific for liver disease, an isolated elevation can suggest cardiac or muscular disease.
- An elevated AST/ALT ratio >2 is more likely to be associated with alcoholic hepatitis. When it is <1.0 it is more likely to be associated with viral hepatitis.
- In acute liver injury (choledocholithiasis, uncomplicated viral hepatitis, ischemic hepatitis), transaminase elevation can be severe, but often resolves within days to weeks. Normalization usually indicates improvement; however, rapid decreases may suggest profound worsening and cell death.
- Non-alcoholic steatohepatitis, non-alcoholic fatty liver, obesity, and thyroid disease can lead to elevated transaminases with or without significant disease.
- Pharmacologic causes include acetaminophen (potentiated with alcohol consumption), NSAIDs, ACE inhibitors, nicotinic acid, and many antibiotics and antifungals.
- Alkaline phosphatase:
- Obstruction of bile ducts leads to increased bile duct epithelial production of alkaline phosphatase (can occur with obstruction of small ducts without clinically significant cholestasis).
- Cholestasis may be diffuse (intrahepatic cholestasis), extrahepatic (gallstones or tumors), localized (cancer), or multifocal (granulomatous disease).
- Cholestasis can be differentiated from osteolytic disease either by fractionation for hepatic alkaline phosphatase or by testing gamma glutamyl transferase levels (increase when hepatic in origin).
- Other causes of elevation include hyperthyroidism, heart failure, and lymphoma.
- When elevated disproportionately to hyperbilirubinemia, may be due to granulomatous or infiltrative liver disease (sarcoid, fungal infection, tuberculosis, lymphoma) or early primary biliary sclerosis or primary sclerosing cholangitis.
- Pitfalls:
- Must be performed while fasting
- Parturients and children have baseline elevated levels (2–3 times normal).
- May indicate excessive alcohol consumption
- Bilirubin:
- A greater than 80% fraction of unconjugated bilirubin suggests hemolysis or Gilbert's syndrome.
- A greater than 50% fraction of conjugated bilirubin suggests hepatocellular dysfunction or cholestasis.
- Albumin:
- Can be decreased in severe systemic disease, liver disease >3 weeks duration, or in rapidly progressive liver disease, where albumin is consumed rapidly
- Lower in parturients
- In the absence of other liver test abnormalities, low albumin is usually due to non-hepatic causes such as proteinuria or malnutrition.
- Prothrombin time:
- Miscellaneous:
- IgM, ANA: Elevated in autoimmune disease
- Low serum copper, uric acid, and ceruloplasmin indicate Wilson's disease.
- Transferrin saturation >60% suggests hemochromatosis.
- Preoperative LFTs can aid with diagnosing disease/hepatic insults and assessing severity.
- Associated disease:
- Infectious diseases (Hepatitis B, C): Care must be taken to minimize practitioner exposure.
- Hepatorenal syndrome: Renal failure associated with hepatic failure. May be reversible or irreversible. Increased morbidity/mortality due to risk of fungemia, uremia, etc.
- Hepatopulmonary syndrome: Elevated pulmonary arterial pressure and increased extracardiac shunting leading to hypoxemia
- Severity-dependent considerations:
- Encephalopathy: Increased risk in the presence of portocaval shunt
- Ascites, increased intra-abdominal pressure: Increased risk of aspiration and desaturation
- Coagulopathy: Transfusion may be indicated in procedures that may not otherwise require blood; patients requiring transfusion are more prone to citrate toxicity.
- Vasoplegia, low SVR: Higher cardiac output required to maintain blood pressure
- Postoperative abnormal LFTs can occur in up to 25–75% of patients without liver disease, and mild elevations are considered typical. Postoperative jaundice typically presents within 2 weeks following surgery and is unusual in patients without liver disease. It is commonly the result of a combination of hypotension, hypoxemia, pigment overload, and sepsis.
5 points, limited life expectancy