Elevated liver enzymes (PATIENT EDUCATION RESOURCES)

Key Facts:
1. Elevations less than five times the upper limit of normal (i.e., about 250 U per L and below) are much
more common in primary care medicine.
2. THE RANGE OF POSSIBLE ETIOLOGIES at this level of transaminase elevation is broad.
3. The MILDLY ELEVATED tests are less specific.
4. Patients with normal ALT and AST levels can have significant liver disease in the setting of chronic
hepatocyte injury.
5. Alcohol is a HEPATOTOXIN.
6. Alcohol is the most widely used cause of hepatotoxicity in the world.
What are liver enzymes?
The liver releases several substances when it is injured. Two of these substances are enzymes called alanine
transaminase (ALT) and aspartate transaminase (AST).
How it is usually tested?
Hepatic transaminase tests such as alanine transaminase (ALT) and aspartate transaminase (AST) often are part
of standard laboratory panels in asymptomatic outpatients, similar to screening tests for blood donors and for
life insurance applicants.

How frequently GPs are to manage this findings?

1. Firstly, the evaluation of an abnormal ALT or AST level in an asymptomatic patient therefore is a
common challenge encountered by primary care physicians.
2. Secondly, according to the American Gastroenterological Association (AGA), 1 to 4 percent of the
asymptomatic population may have elevated serum liver chemistries.
3. Physicians who have more patients with obesity, diabetes, and hyperlipidemia will have to address this
issue more often.
4. Given the frequency of this problem, physicians should develop an informed approach to the
investigation of transaminase elevations.
5. An audit of primary care practices found that these abnormalities are not always investigated
appropriately and that opportunities to intervene in treatable cases sometimes are missed.
6. The AGA recently published a technical review and a position statement on the evaluation of liver
chemistry tests.

What are the recommendations of AGA on how to address an abnormal liver function tests?
 An algorithmic approach to evaluating mildly abnormal liver functions is recommended.
 In the asymptomatic patient WITH NEGATIVE SERUM TESTING and MILD TRANSAMINASE ELEVATIONS,
a period of LIFESTYLE MODIFICATION can be tried.
o IF ABNORMALITIES PERSIST at the six-month follow-up visit, an ULTRASONOGRAPHY of the
liver is the recommended imaging modality.
 The AST/ALT ratio is only SOMEWHAT HELPFUL IN DIAGNOSIS.
 The ratio of AST to ALT has some clinical utility, but has important limitations.
o In many forms of acute and chronic liver injury or steatosis the ratio is less than or equal to 1.
o This is particularly true in patients with hepatitis C.
 An AST/ALT ratio greater than 2 characteristically is present in alcoholic hepatitis.
 A recent study of 140 patients with biopsy confirmed nonalcoholic Steatohepatitis (NAFLD) or
alcoholic liver disease (AFLD) showed:
o mean AST/ALT ratio in NAFLD patients was 0.9.
o mean AST/ALT ratio in AFLD was 2.6.
o of patients with an AST/ALT ratio of 1.3 or less, 87 percent had NAFLD at last.
o The severity of NAFLD (assessed by the degree of fibrosis) increased as the AST/ALT ratio
soared.
 o in patients with cirrhosis related to NAFLD, a mean ratio of 1.4 was found.
o Wilson’s disease can cause the AST/ALT ratio to exceed 4.
o
Are liver transaminase levels a proper screening modality?
 ALT and AST are not useful screening tests in AN OTHERWISE HEALTHY POPULATION.
What do these liver transaminases show?
 ALT and AST are two of the most reliable markers of HEPATOCELLULAR INJURY or necrosis.
 Their levels CAN BE ELEVATED IN A VARIETY OF HEPATIC DISORDERS.
 Of the two, ALT IS THOUGHT TO BE MORE SPECIFIC FOR HEPATIC INJURY because it is present mainly
in the cytosol of the liver and in low concentrations elsewhere.
 AST has cytosolic and mitochondrial forms and is present in tissues of the liver, heart, skeletal muscle,
kidneys, brain, pancreas, and lungs, and in white and red blood cells.

What causes elevated ALT and AST levels?

There are many causes of mildly elevated ALT and AST levels. The most common causes are nonalcoholic
fatty liver disease (NAFLD) and alcoholic liver disease. In NAFLD, the liver has more fatty tissue in it than
normal. Regular or heavy alcohol use can also hurt the liver and increase liver enzymes. Other medical
conditions can increase liver enzymes, like hepatitis B or C and a condition that runs in families called
hemochromatosis. Using certain medicines and over-the-counter supplements can also increase liver enzymes.

What are the symptoms?

People with mild elevations in liver enzymes usually do not have symptoms.

What will my doctor do?

Your doctor will ask you questions and examine you to try and find out why your liver enzymes are elevated.
He or she may also do blood tests. A scan of your liver, called an ultrasound, might help your doctor find a
cause.
How is it treated?
It depends on what is causing your liver enzymes to be elevated. If your doctor thinks you have NAFLD, you
will need to make lifestyle changes. These changes include eating a healthier diet, exercising, losing weight, and
limiting alcohol and sugary foods and drinks.
What if a cause isn't found or my liver enzymes stay elevated?
Your doctor may do further testing. You may need to see a specialist who can check for less common causes.
Your doctor may also take a small piece of your liver for testing. This is called a biopsy.
This handout is provided to you by your family doctor and the American Academy of Family Physicians. Other
health-related information is available from the AAFP online at (http://familydoctor.org).

How serious is elevated liver transaminase levels?

Most of the time, elevated liver enzymes don't signal a chronic, serious liver problem.

How these abnormal levels are discovered?

Elevated liver enzymes might be discovered during routine blood testing.

How much most of the time these levels are higher than normal?
In most cases, liver enzyme levels are only mildly and temporarily elevated.

What might cause a higher level of liver transaminases?

Mild elevations in liver chemistry tests such as alanine transaminase and aspartate transaminase can reveal
serious underlying conditions or have transient and benign etiologies.
More common causes of elevated liver enzymes include:
1. Hepatic causes of Moderately Elevated Liver Enzymes (MELE)
a. Common causes:
i. Alcohol
ii. Viral Hepatitis
1. Acute
2. Chronic (B and C)
iii. Cirrhosis
iv. Steatohepatitis
v. Drug Induced
b. Less common causes:
i. AI hepatitis:
ii. Storage diseases
1. Iron (Hemochromatosis)
2. Copper (Wilson’s disease)
3. Alpha1-antitripsine Deficiency
2. Non- Hepatic Causes:
a. Celiac Disease
b. Hemolysis
c. Myopathy
d. Hyperthyroidism
e. Strenuous exercise
 Pharmaceuticals: (Medication and supplements)
o Pain medications
 OTCs
 Prescription:
 Statin drugs
o Diseases:
 Heart Failure
 NAFLD
 Obesity
 Viral Infection of Liver: Hepatitis A, B, C
 Viral Systemic Infection by CMV
 Viral Systemic Infection by IMN
 Sepsis
 Storage diseases:
 Wilson’s Disease
 Hemochromatosis
 Steatosis or steatohepatitis
 Metabolic Diseases:
 Hypercholesterolemia
 Cancer
 Autoimmune diseases
 Celiac Disease
 AI Hepatitis
 Polymyositis
 Toxic Hepatitis:
 Drugs
 Toxins
 Liver Failure or CIRRHOSIS
When to see a doctor?
If a blood test reveals you have elevated liver enzymes, ask your doctor what the results might mean.

What might happen then?

Your doctor will take a thorough history from you.
As some of underlying causes have genetic correlation, your doctor will take FH.
He will ask about your DH, Sexual History and Immunization status as well.
When the history and physical examination do not reveal the cause, your doctor might take another step.

Your doctor might suggest you undergo other tests and procedures to determine what's causing your elevated
liver enzymes.

Mildly Elevated Liver Transaminase Levels in the Asymptomatic Patient

Mildly Elevated Liver Transaminase Levels: Causes and Evaluation
Causes and Evaluation of Mildly Elevated Liver Transaminase Levels
Evaluation of Elevated Serum Transaminase Levels
Guidelines on the management of abnormal liver blood tests
Liver function tests
Liver Function Tests
Patterns of abnormal LFTs and their differential diagnosis

ALT is expected to be no more than 55 IU/L.

SGPT is another name for ALT.
ALT is a cytosolic enzyme.
ALT increases in Hepatitis.
The ALT/AST ratio will increase in hepatitis.
The ALT/AST ratio will decrease in cirrhosis/FALD.
ALP, a liver function test item, is released from bone and biliary epithelium.
GGT is also released from biliary epithelium.
In biliary pathologies both ALP and GGT rise.
Biliary pathologies include Infiltration, Congestion and Obstruction.
In case ALP soars but GGT remains intact, suspect bone pathologies.
ALP from bone and biliary sources have various distinguishable isoenzymes.
Evaluate risk factors for hepatitis as the cause of elevated liver function tests.
Elevated Liver Enzymes
Liver enzyme alteration: a guide for clinicians - NCBI
Liver Function Tests

In an asymptomatic patient with elevated liver transaminase levels: