What is being tested?

This test measures the amount of smooth muscle antibodies (SMA) in the blood. SMAs are proteins produced by the body’s immune system to work against its own cytoskeletal proteins. The production of SMA is strongly associated with chronic autoimmune hepatitis but may also be seen in other forms of liver disease and with other autoimmune disorders such as primary biliary cirrhosis. Autoimmune hepatitis presents as an acute or chronic inflammation of the liver that is not caused by another factor (such as a viral infection, drug, toxin, hereditary disorder or alcohol abuse). It can lead to cirrhosis (liver damage and scarring) and, in some cases, to liver failure.

There are 3 subtypes of SMA antibodies, which reflect their staining pattern when measured by indirect immunofluorescence: SMA-V, SMA-VG and SMA-VGT, the latter often called just SMA-T.

In adults, the SMA-T pattern is strongly correlated with auto-immune hepatitis, though when treated any pattern may be present (the antibodies may even disappear).

In children, the antibodies may be present at lower level (titre) than adults and the SMA-V pattern may also indicate autoimmune hepatitis. In adults, SMA-V or VG often indicates a viral infection (hepatitis C), or other auto-immune condition e.g. SLE.

Autoimmune hepatitis can be found in anyone at any age, but about 80% of those affected are women. More than 80% of patients with this disorder will have SMA, either alone or along with antinuclear antibodies (ANA).

Anti-F-actin is an antibody targeted at actin, a specific cytoskeletal protein. Some recent studies suggest that it is a more specific test than SMA for diagnosing autoimmune liver disease, with about 52% to 85% of those affected having the anti-F-actin antibody. Anti-F-actin antibody measurements are only available in a few laboratories and these assays lack sensitivity at present.

How is it used?

The SMA test is primarily ordered along with antinuclear antibodies (ANA) to help diagnose autoimmune hepatitis. Other autoantibodies, such as liver-kidney microsomal type 1 (LKM1) antibodies and antimitochondrial antibodies (AMA), may also be ordered to help diagnose autoimmune hepatitis and distinguish it from other causes of liver disease or injury.

When is it requested?

This test and the ANA test are ordered when a doctor suspects that the patient has autoimmune hepatitis. They are usually ordered when a patient presents with symptoms such as fatigue and jaundice (yellowing of the skin and eyes) along with abnormal findings on liver tests (such as aspartate aminotransferase (AST) and/or bilirubin), results that may be found during routine blood tests.

SMA and ANA are usually ordered following, or sometimes with, a variety of tests that are used to help diagnose and/or rule out other causes of liver injury. These causes can include infections (such as viral hepatitis), drugs, alcohol abuse, toxins, genetic conditions, metabolic conditions and primary biliary cirrhosis.

An anti-F-actin test may be ordered as well as SMA when the doctor wants to screen for autoimmune hepatitis. This test is relatively new. The ultimate clinical utility of the anti-F-actin test has yet to be established. Anti-F-actin antibodies may also be present in coeliac disease.

What does the result mean?

When significant amounts of SMA and ANA are present in the blood, the most likely cause is autoimmune hepatitis. When both are present, then systemic lupus erythematosus can be essentially ruled out (ANA will be positive with lupus, but ASMA will not).

When anti-F-actin antibodies are present in significant quantities in a patient with clinical signs of autoimmune hepatitis, then it is likely that the patient has the condition. In most cases, if the anti-F-actin is positive, the SMA will also be positive. Since actin is only one of several cytoskeleton proteins, it is possible for a person to have smooth muscle antibodies even when the anti-F-actin test is negative.

Is there anything else I should know?

Concentrations of SMA may be lower in children and in those with compromised immune systems, and levels may vary over the course of the disease. Up to twenty percent of patients with autoimmune hepatitis will not be positive for SMA, ANA or LKM1 antibodies.

Small amounts of SMA may be present, along with AMA, in up to fifty percent of patients with primary biliary cirrhosis and may be found in other conditions such as infectious mononucleosis and some cancers. Anti-actin antibodies may be present in about twenty two percent of patients with primary biliary cirrhosis.

The presence of SMA, anti-F-actin antibodies and ANA are highly suggestive of autoimmune hepatitis but not diagnostic. When significant titres of both SMA and ANA are present and the doctor suspects autoimmune hepatitis, then a liver biopsy may be performed to look for characteristic signs of damage and scarring in the liver tissue.

Common questions

• Will SMA ever go away?

If it is due to a temporary condition, such as infectious mononucleosis, SMA may drop below detectible levels once the condition has resolved. If SMA is produced because of autoimmune hepatitis, then it will be present throughout the patient’s life, although levels may vary over time. The SMA level is not a reliable indicator of liver disease. Treatment for the liver disease will affect the level of SMA.

• Can I have more than one cause of hepatitis?

Yes. For instance, autoimmune hepatitis can co-exist with a viral hepatitis (such as hepatitis C) and can be exacerbated by liver damage caused by alcohol abuse. Since the treatment of hepatitis depends on the cause, it is very important that your doctor understands the underlying cause(s) of your condition.

• How fast does autoimmune hepatitis progress?

The course and severity of autoimmune hepatitis is hard to predict. It may be acute or chronic. Many patients will have no or few symptoms for many years and are diagnosed when routine liver tests are abnormal. Occasionally, people present with severe acute liver failure from autoimmune hepatitis.

More information

RCPA Manual: Smooth muscle antibody