Blood tests: How to read and understand the results of a liver function test

What is the role of the liver?

The liver has a crucial role of synthesis and regulation. It is involved in lipid metabolism, the assimilation and purification of fats via bile, carbohydrate metabolism (glycogen storage and formation of neo-glucose), the synthesis of blood proteins (hemoglobin, albumin and coagulation factors), the immune system by filtering germs of intestinal origin and the detoxification of many substances.

What are some of the different types of liver diseases?

Liver diseases affect all ages and a real public health issue. Liver diseases are numerous and the causes are varied:

• Viral hepatitis (HAV, HBV, HCV), autoimmune, drug-induced and alcoholic hepatitis; 

• Liver cancers; 

• Cirrhosis and hepatic fibrosis;

• Biliary lithiasis; 

• Hemochromatosis (excessive iron absorption in the intestines with serious repercussions on the liver);
• Wilson's disease (build-up of copper in the liver and brain);
• Amyloid polyneuropathy

The main manifestations are jaundice, pruritus (itching), encephalopathy (brain damage), signs of GI bleeding and portal hypertension, and signs of ascites (accumulation of fluid in the abdominal cavity).

Blood tests

CBC (Complete blood count):

Standard values

WBC (White blood cell count)

3.4-9.6 billion cells/L

RBC (Red blood cell count)

Female normal range: 3.92-5.13 trillion cells/L

Male normal range: 4.35-5.65 trillion cells/L

Hemoglobin (Hb)

Female normal range: 11.6-15 g/dL

Male normal range: 13.2-16.6 g/dL

Hematocrit (Hct)

Female normal range: 35.5-44.9%

Male normal range: 38.3-48.6%

Platelet Count (PLT)

Female normal range: 157-371 billion/L

Male normal range: 135-317 billion/L

Why is a full blood test done?

A full blood test is essential to detect anemia (low red blood cell and hemoglobin levels) which can aggravate the patient's condition, and it will also be used to detect an abnormality in blood coagulation.

Hemostasis screening tests

Standard values: Please note that the reference values may change for a patient undergoing long-term anticoagulant therapy

Why are hemostasis screening tests done?

The liver is responsible for the synthesis of proteins and coagulation factors. In case of liver diseases, the liver may have difficulty in synthesizing these factors. As a result, there may be a risk of hemorrhaging (GI bleeding in particular) and bruising, which must be prevented.

Prothrombin Time (PT)

Standard values

PT (Prothrombin Time)

25-35 seconds

Why this test?

The prothrombin time (PT) evaluates the extrinsic pathway and common pathway of coagulation and is able to identify anomalies in coagulation factors I (fibrinogen), II (prothrombin), V (proaccelerin), VII (proconvertin) and X (Stuart-Power factor). It measures the time it takes for a blood clot to form in a given patient. In an ill patient, this time tends to be longer due to a deficiency in coagulation factors (a patient will take longer to clot). This is the same test as the PT expressed in units of time. Increase PT can indicate liver damage, but may also be higher if you're taking certain blood-thinners, such as WARFARIN.

International Normalized Ratio (INR)

Standard values

Target INR: 2.0-3.0 in general for patients on anticoagulant drugs

Note: target INRs are adapted according to individual situations and patient profiles, e.g. for patients at high risk of clot formation, the target INR is 3.0-4.0.

Why this test?

It is the International Normalized Ratio, which is an indicator of blood coagulation, and is in fact the clotting time ratio of a patient and a control value taken from the average PT from 20 or more healthy subjects. INR is used to determine the effective dose of medication that keeps the patient in the therapeutic zone and limits the risks inherent to the treatment. The lower the INR (below the target), the less fluid the blood is and vice versa. In all cases, it is imperative to be seen by a specialist (cardiologist, nephrologist, rheumatologist, endocrinologist, etc.).

Coagulation factors

Coagulation factors have a short life span (half-life of a few hours), so they are reliable indicators impaired liver synthesis function.

Factor V

Standard values

50-150 %

Why this test?

Factor V is a coagulation factor exclusively synthesized in the liver. In the case of severe liver dysfunction, a decrease in the level of factor V is a sign of severe disease: for example, in the case of liver failure, it is often less than 50% (like PT).

Liver blood tests (also known as liver function tests)

Aminotransferases: ALAT, ASAT and LDH

Transaminases or aminotransferases are enzymes (proteins) found in the liver cells (hepatocytes) which are involved in breathing and cellular function. They are a helpful indicator of liver damage, as they indicate the degree of inflammation present in the liver. When liver cells are damaged, these enzymes leak into the blood stream.

Alanine aminotransferase (ALT)

Standard values

4-36 units/L

Why this test?

ALT is found in the liver and kidney cells and in smaller quantities in skeletal muscle and red blood cells. It is the best indicator of cytolytic hepatitis (a liver disease causing cell destruction) and can reach up to 10 times its normal value (in the case of viral or drug-induced hepatitis) or even 1000 times its normal value (in the case of fulminant hepatitis, a stage of acute liver failure and the ultimate stage of severity where the only therapeutic option remains liver transplantation).

Aspartate aminotransaminase (AST)

Standard values

0-36 units/L or 0-0.58 μKat/L

Values may be lower in females than in males

Why this test?

AST is found in skeletal muscle and heart cells, in red blood cells and finally in liver cells. Its increase is a sign of cytolysis (cell destruction) of the liver and heart. Most often it is lower than the ALT level, except in the case of alcoholic-related liver disease. Indeed, in alcoholics, the AST level is higher than the ALT level.

Lactate Dehydrogenase (LD)

Standard values

338-610 U/L

Why this test?

Lactate dehydrogenase is an enzyme found in almost all body tissues. Normally its concentration in the blood is low as it is contained within tissue cells. When tissues are damaged or destroyed they release LD into the bloodstream. Because of this, the LD level is a non-specific marker for cell damage. This test, or assay, can be used in the diagnosis of pulmonary, cardiac and even hematological (blood) diseases.

Other enzymatic assays for liver function tests: GGT and ALP

Gamma-glutamyl transferase (GGT)

Standard values

Male and female over 45 years: 8-38 U/L

Female younger than 45 years: 5-27 U/L

Why this test?

GGT is an enzyme mainly found in the liver but also in the pancreas and kidneys. They enable the transfer of amino acids (necessary for protein synthesis) inside the cells. When the liver is damaged, GGT leaks into the bloodstream and its concentration in the blood increases. Because of this, GGT is a good marker for liver conditions such as cirrhosis, cholestasis, hepatitis and alcoholism.

Alkaline phosphatase (ALP)

Standard values

38 - 126 U/L

Values may vary according to the laboratory and the patient profile

Why this test?

Alkaline phosphatase is an enzyme found in several tissues: bones, intestines, the placenta and kidney tubules, but also the bile ducts. There is a physiological (normal) elevation of ALP in children and adolescents with growing bones (due to an increase in the activity of bone-forming cells). In adults, this increase can be a sign of bone disease (Paget's disease). ALP is also increased in pregnant women due to the presence of the placenta. In addition, a concurrent increase in ALT, AST, GGT and ALP is strongly suggestive of liver damage.

For example, the diagnosis of cholestasis (decrease or stoppage of biliary secretion) is biologically based on the increase in ALP and GGT.

Bilirubin (nonconjugated, conjugated, total)

Standard values

Unconjugated ("indirect") bilirubin

0.2-0.8 mg/dL or 3.4-12.0 µmol/L

Conjugated ("direct") bilirubin

0.1-0.3 mg/dL or 1.7-5.1 µmol/L

Total bilirubin (indirect + direct)

0.3-1.0 mg/dL or 5.1-17 µmol/L

Values may vary according to the laboratory

Why this test?

Bilirubin is a waste product mainly produced in the breakdown of heme, a component of hemoglobin (the protein that makes up red blood cells). The level of "total bilirubin", which is the sum of the levels of indirect (nonconjugated) and direct (conjugated) bilirubin, is measured. Bilirubin is "unconjugated" or "direct" before it has passed through the liver and "conjugated" or "indirect" after (through the conjugation process in the liver). Conjugated bilirubin is released into the bile and then excreted in the urine and stool. In healthy individuals, it is not present in the blood.

In the case of biliary tract obstructions, conjugated bilirubin passes into the bloodstream. A rise in bilirubin can indicate a bile disorder (gallstones, biliary lithiasis, cholestasis or biliary tumor), hepatitis or cirrhosis or even hemolysis (excessive and abnormal destruction of red blood cells). It is yellow in color and is responsible for jaundice when it accumulates abnormally in the blood. Jaundice is the yellow coloration of the skin and mucous membranes, nails and the whites of the eyes. Dark urine and discolored stool can also be observed.

Protein electrophoresis: why measure blood proteins?

Proteins synthesized in the liver

Albumin (ALB)

Standard values

3.5-5.5 g/dL

Why this test?

Albumin is the most abundant protein in the blood (60% of total protein) and is synthesized by the liver. It carries multiple proteins in the bloodstream, including conjugated bilirubin. During pregnancy, albumin levels can be lowered due to blood dilution. Apart from this particular case, a decrease may indicate liver damage.

Haptoglobin

Standard values

50-220 mg/dL

Why this test?

Haptoglobin is a synthetic liver protein, the decrease of which may indicate liver fibrosis (scarring of the liver cells after their destruction), excessive hemolysis (unexplained destruction of red blood cells) or even liver failure. This assay is used to diagnose and evaluate stages of fibrosis during tests such as the FibroSure or ActiTest. It should also be noted that levels of this protein increase with inflammatory syndromes (as in the case of an infection).

α-1-acid glycoprotein (AGP)

Standard values

60–120 mg/dL

Why this test?

Alpha-1-acid glycoprotein, also known as orosomucoid, is a synthetic hepatocyte protein (hepatocytes are the cells of the liver) whose secretion into the bloodstream is stimulated by inflammatory reactions. In the case of an inflammatory syndrome, a decrease of its concentration in the blood combined with a decrease in haptoglobin leads to liver failure.

Similarly, other synthetic liver inflammation proteins such as α2-macroglobulin or α1-antitrypsin can reveal liver disease.

Alpha-fetoprotein (AFP)

Standard values

< 8.0 ng/mL

Why this test?

Alpha-fetoprotein is present in fetal blood and its levels are used to monitor the development of fetal malformations during pregnancy (such as Down syndrome, for example). As part of a liver function test, this assay can be useful in cases of suspected hepatocarcinoma (HCC). It is not specific to the liver and may be used to monitor the recurrence of certain cancers (of the ovaries or testes).

Electrolyte test: Monitoring electrolytes in the blood

Ammonia

Standard values

10-80 mcg/dL or 6-47 μmol/L

Why this test?

High levels of ammonia in the blood may be a sign of hepatic encephalopathy (impaired brain function, confusion or unexplained drowsiness). The condition occurs when the liver is too diseased or damaged to process ammonia. Ammonia builds up in the blood and reaches the brain.

Lipid panel

Standard values

Triglycerides: <150 mg/dL

Total cholesterol: 125-200 mg/dL

HDL cholesterol: >1 mmol/L in men, >1.2mmol/L in women

LDL cholesterol: <100 mg/dL

Why these tests? 

A lipid profile or panel is often requested in parallel with a liver test: It is important to know that two thirds of the body's cholesterol is synthesized by the liver. A liver abnormality can have repercussions on this test.

Normal values

Apolipoprotein A1 (Apo-A1)

Normal range for females: >140 mg/dL or 1.4 g/L

Normal range for males: >120 mg/dL or 1.2 g/L

Why this test?

More specifically, Apo-A1 can be measured. It is a cholesterol transport protein synthesized by the liver, the release of which is diminished in cases of hepatic fibrosis. This liver damage is manifested by a decrease in the level of Apo-A1 in the blood.

Conclusion: 

It is recommended in the case of liver damage to avoid any substance identified as hepatotoxic (damaging or destructive to liver cells): in particular alcohol and certain drugs (such as paracetamol) should be avoided. There is also controversy about plant-based supplements, the increased consumption of which has been shown to be hepatotoxic. For example, synthetic anabolic-androgenic steroids, glue thistle, green tea, senna and even vitamin A are subject to precautionary measures for use in patients prone to liver disease.

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