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Lab test update - ALT

Clinical biochemist Dr Berenice Lopez uses a primary care case history to discuss the use of alanine aminotransferase testing

Clinical biochemist Dr Berenice Lopez uses a primary care case history to discuss the use of alanine aminotransferase testing

How common is asymptomatic elevated ALT?

41209551About 6% of asymptomatic patients may have an abnormality of ALT picked up on screening but this will vary across the population depending on factors such as the prevalence of obesity and alcohol use.

What is the likeliest cause of an asymptomatic elevated ALT result?

In the UK, the top three causes are:

• alcoholic liver disease (ALD)

• non-alcoholic fatty liver disease (NAFLD)

• viral hepatitis.

About four in every 1,000 of the general population in England may be chronically infected with hepatitis C.

NAFLD is an increasing problem reflecting the rising levels of obesity. It is thought to reflect the liver component of the metabolic syndrome and may be an independent risk factor for cardiovascular disease. Essentially, fat accumulates in the liver cells and causes leakage of ALT.

In most patients, this follows a benign course, but in some patients this accumulation of fat triggers an inflammatory response causing non-alcoholic steatohepatitis (NASH), which may then progress to cirrhosis and hepatocellular carcinoma. Unfortunately, there is no good way yet of identifying which patients have benign fatty liver and which have more serious disease.

This patient is obese, hyperlipidaemic and is also exceeding the recommended limit of weekly alcohol intake for men of 21 units. He is not on any hepatotoxic drugs and in the absence of other risk factors or clinical signs of liver disease, he is most likely to have fatty liver as a consequence of excess alcohol and the metabolic syndrome.

Is it best to suggest weight loss, alcohol reduction or medication withdrawal as a first step – in which case, when should ALT be repeated?

This boils down to how worried you should be when faced with a single abnormal result. Much depends on the pre-test probability of disease. Generally though, a significant number of isolated elevated ALT values may fall within the reference range on retesting. This is likely to reflect the statistical phenomenon of regression to mean. Therefore, retesting within a few weeks or so, to distinguish a one-off result from stable and progressive increases, is sensible. This man should be advised to reduce his alcohol intake in any case.

When should further investigations be arranged?

If ALT remains elevated on retesting, make sure you have taken a careful history. Are there any other risk factors for liver disease? Look for signs of chronic liver disease.

A liver work-up is mandatory for ALT elevations associated with risk factors for, or clinical evidence of, liver disease.

But the problem GPs face is that risk factors such as illicit drug use and sexual practices may be difficult to elicit and patients with compensated liver disease may not have any clinical signs.

Given that most liver disease is treatable if identified early and that liver diseases may co-exist, there is an argument for performing a liver work-up in all patients with confirmed, unexplained elevations of ALT. A diagnosis can actually be established non-invasively in most (see box at the end of this article).

But realistically, in the UK most patients like this man are likely to have NAFLD or ALD and this strategy arguably could result in overinvestigation.

In patients who appear to only have risk factors for NAFLD or ALD and whose ALT levels are less than three times the upper limit of normal, a six-month trial of an appropriate intervention – weight loss, control of lipids and moderation of alcohol intake – followed by a liver work-up if ALT levels do not normalise over this time may be a more pragmatic approach.

Patients with confirmed elevations of ALT above three times the upper normal limit are more likely to have significant hepatitis. A liver work-up should be arranged and the patient discussed with, or referred to, hepatology.

Is it reasonable for him to be started on a statin despite the elevated ALT?

Yes. He is at a higher risk from morbidity and mortality secondary to cardiovascular disease than from statin hepatotoxicity. Current thinking is that patients with compensated cirrhosis, chronic liver disease, NAFLD or NASH may safely receive statin drugs. There is evidence, in fact, that treatment with a statin may actually help.

Dr Berenice Lopez is specialist registrar in clinical biochemistry and metabolic medicine at North Bristol NHS Trust and a part-time GP

Competing interests: none declared

For more information on the use of lab tests in primary care, go to which has 120 clinical scenarios from general practice.

Key points ALT Liver work up

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