Abnormal liver function tests

What the tests actually measure

The name is a misnomer, and it is worth clearing up first. Most of what is on a liver panel does not measure how well the liver is functioning. It measures whether liver cells are being damaged, and whether bile is flowing. The international guidance now prefers the term liver chemistries or liver tests for that reason.

Four results do most of the work:

• ALT and AST are enzymes that live inside liver cells. When those cells are injured, the enzymes leak into the blood. A rise means damage is happening, not that the liver has stopped working.
• ALP, alkaline phosphatase, rises when bile flow is obstructed, whether inside the liver or in the ducts leading out of it. It also comes from bone, so a raised ALP is not always about the liver at all.
• Bilirubin is the pigment that makes someone yellow when it is high enough. It is split into two forms, and which one is raised points in quite different directions.

GGT often appears alongside them. It is sensitive and not specific: it rises with alcohol, with fatty liver, with several medicines and with bile duct problems, so on its own it rarely settles anything. A raised GGT with everything else normal is usually not a liver disease.

The results that genuinely do measure function are the ones that are easy to overlook: albumin, the INR and the platelet count. A liver that is failing makes less albumin and fewer clotting factors. Those three carry more weight than a moderately raised ALT.

Why the pattern matters more than the number

The first question a specialist asks is not how high, but which pattern. Two results of exactly the same size lead to entirely different investigations depending on what is raised alongside them.

• A hepatocellular pattern means ALT and AST are raised out of proportion to ALP. Something is injuring liver cells.
• A cholestatic pattern means ALP is raised out of proportion to ALT and AST. Bile is not flowing properly, either because a duct is blocked or because the small ducts inside the liver are diseased.
• A mixed pattern is exactly what it sounds like, and is common.

The height of the rise then narrows it further. A mild rise, up to two or three times the upper limit, is the commonest picture and usually reflects fatty liver, alcohol or a medicine. A rise into the hundreds points towards a virus, a drug reaction or autoimmune hepatitis. A rise into the thousands is a short list: a severe drug injury, acute viral hepatitis or a period where the liver was deprived of blood flow.

What usually turns out to be the cause

In a general Australian population, a short list accounts for most abnormal results.

Fatty liver

By a wide margin the commonest. Fat accumulating in liver cells, associated with weight, insulin resistance, type 2 diabetes and high cholesterol. Most people with it have normal or only mildly abnormal tests, which is one reason it is missed. It has its own page, covering what it means and what changes it: fatty liver disease.

Alcohol

Often contributing even where it is not the whole answer, and frequently under-reported, not out of dishonesty but because standard drink sizes bear little resemblance to what is actually poured at home. An AST higher than ALT is a pattern that raises the question. The useful conversation is about quantity and pattern rather than about labels.

Medicines and supplements

A long list, and the ones people forget to mention are the ones bought without a prescription. Paracetamol in ordinary doses is safe for the liver, but high doses or repeated doses on an empty stomach are not. Anti-inflammatory painkillers, some antibiotics and a number of herbal and bodybuilding supplements can all injure the liver. Bringing the actual packets to the appointment is more useful than trying to recall the names.

Viral hepatitis

Hepatitis B and hepatitis C are both testable and both treatable, and both can be present for decades without symptoms. Anyone born in a country where hepatitis B is common, or who has ever injected drugs or had a blood transfusion in Australia before February 1990, when screening of the blood supply began, should be tested rather than assumed to be negative.

Iron overload

Haemochromatosis is the commonest inherited disorder in people of northern European ancestry, which describes a large share of the Australian population. It causes iron to accumulate over decades, and it is diagnosed on a blood test and confirmed genetically. It matters because it is straightforward to treat once it is found, and because the damage it causes is not reversible.

Autoimmune and less common causes

Autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, Wilson's disease and alpha-1 antitrypsin deficiency are each uncommon, and collectively they are not. Most are found by blood tests that are part of a standard work-up rather than by anything exotic.

Causes outside the liver

A raised ALP can come from bone. A raised AST can come from muscle, including after hard exercise or a fall. An isolated rise in unconjugated bilirubin, with everything else normal, is usually Gilbert's syndrome. Estimates of how common it is range from about 1 in 50 to about 1 in 10, it is roughly twice as common in men, and it causes nothing and needs no treatment. It is worth naming because it causes a lot of avoidable worry.

How the cause is worked out

The sequence is fairly standard, and most of it happens before anyone is referred.

1. Repeat the test. A single mildly abnormal result in someone well is sometimes just that. A repeat in a few weeks, with the pattern confirmed, avoids a great deal of unnecessary investigation.
2. Take the history properly. Alcohol, every medicine and supplement, weight history, diabetes, family history and country of birth. This step identifies the cause more often than any test does.
3. The blood panel. Hepatitis B and C serology, iron studies, autoimmune antibodies, immunoglobulins and the tests that genuinely measure function: albumin, INR and platelets.
4. An ultrasound. Shows fat in the liver, gallstones, duct dilatation and the texture and size of the liver itself. It is the right first scan and often the only one needed.
5. Assessing for scarring. This is the step that decides what happens next, and it is covered below.

Where all of that is unrevealing and the abnormality persists, further imaging or a liver biopsy may be considered, to establish a diagnosis, to judge how advanced things are, or where more than one cause seems to be in play.

The question that actually matters

Once a cause is identified, the question that changes management is not how abnormal the numbers are. It is how much scarring has already happened.

This catches people out, because the two are only loosely related. Someone can have tests barely outside the normal range and significant fibrosis underneath, and someone else can have a markedly abnormal ALT with a structurally normal liver. Nothing on the blood panel reports it directly.

It is assessed in two main ways. Scores calculated from routine blood results give a first estimate at no cost. Where those are indeterminate or raised, a specialised ultrasound that measures the stiffness of the liver gives a much better answer. It takes a few minutes, involves no needle and no radiation, and it is the single most useful test in this area.

The reason it matters is that early scarring can improve or reverse when the cause is addressed, while advanced scarring changes what needs to happen next, including whether someone needs monitoring for the complications of cirrhosis.

When to be seen sooner

Most abnormal liver tests are not urgent. These are the exceptions:

• Yellowing of the skin or the whites of the eyes.
• Dark urine with pale stools.
• Persistent itch without a rash.
• Abdominal swelling, or swelling of the legs.
• Confusion or unusual drowsiness.
• Vomiting blood, or black tarry stools.
• Any liver result in the thousands.
• A low albumin, a raised INR or a falling platelet count alongside the abnormality.

The last of those is the one most often overlooked. A platelet count that has been quietly drifting down over several years, alongside mildly abnormal liver tests, is a recognised early sign of significant scarring, and it is visible on blood tests that were taken for other reasons.

What to expect after a referral

The first appointment is mostly conversation. The history identifies the likely cause more often than any single test, so expect detailed questions about alcohol, medicines and supplements, weight over time, other conditions and family history. Bringing the previous results matters, because the trajectory over years is more informative than any one reading.

Most people leave with a plan that involves a small number of blood tests, an ultrasound if one has not been done, and an assessment of scarring. Most causes are managed without any procedure.

For the large group whose answer is fatty liver, the treatment is not a tablet, and the change that matters most is sustained weight loss, which has a greater effect on the liver than on almost any other organ. That is covered on the fatty liver page, and the weight management page covers what help is available with it.

Where abnormal liver tests are assessed in Sydney

A/Prof Viraj Kariyawasam is a consultant gastroenterologist and hepatologist. Liver blood tests that have come back abnormal are among the commonest reasons for a referral, and they are assessed at consultation in Norwest, Rouse Hill, Pennant Hills and Macquarie Park.

Where a gastroscopy or a liver assessment with imaging is needed, it is arranged at Norwest Private Hospital, Macquarie University Hospital and Pennant Hills Day Surgery. A referral from your GP is needed for a consultation.