Investigating abnormal liver tests

Deciding how to follow up an abnormal liver test result is difficult for GPs, say Dr Belinda Keogh and Dr James Neuberger

With the introduction of autoanalysers, GPs now have access to a wide range of liver function tests (LFT). As a result they are faced with unexpectedly abnormal test results more often than in the past.

Abnormal test results require the GP to decide whether to investigate further or ignore it. Both options present pitfalls. The first may cause the patient unnecessary worry and additional expense to the NHS while the second may lead to a serious condition being missed at a treatable stage.

Interpreting results
An estimated 15 per cent of LFTs are abnormal in at least one analyte. A GP must decide whether the initial abnormal test result is real and accurate or a statistical anomaly.

The standard battery of analytes measured when a GP requests an LFT varies from laboratory to laboratory, and the range defined as normal also varies.

It is calculated using measurements taken from healthy people, with a cut-off point two standard deviations above and below the median. This means that some healthy people will have LFT analyte levels outside the normal range.
Conversely, levels within the normal range do not necessarily mean that the patient is healthy. A Korean study showed that patients who had a high normal level of aspartate aminotransferase (AST) had a greater risk of dying than those with a low normal value.

Abnormal liver tests usually indicate the presence of liver disease, and specific investigations are needed to determine the cause. It is important that abnormal LFTs are not ignored, because up to 20 per cent of people with unexpected abnormal liver tests have been found by researchers to have treatable conditions.

Reasons to investigate
The main reason to investigate an abnormal LFT is to detect treatable diseases.

Further testing can also identify cases where lifestyle factors such as obesity are contributing to disease as well as those who need to implement hygiene measures to prevent spreading infection. Medication changes may also influence LFTs.

In some circumstances abnormal LFTs may also reveal a need for genetic screening in family members.

The action required will depend on the clinical situation. In asymptomatic patients, the first step is to repeat the LFT and take a full history.

However, if the patient were truly asymptomatic it is unlikely that LFTs would have been requested. When taking the history, it is important to ask the patient about all drug use, including medications that they might have borrowed from family or friends, vitamins and herbal remedies, previous blood transfusions, transfusions and sexual history.

A full alcohol history should be taken and other lifestyle factors should be considered including possible exposure to hepatitis or environmental toxins, family history of liver disease and possible pregnancy.

LFTs are most often requested in the non-specifically unwell patient. Lethargy is a common symptom presenting in both general practice and hospital medicine. It may have many causes, but marked lethargy can be a sign of primary biliary cirrhosis and may be suspected on the basis of abnormal LFTs and confirmed by an anti-mitochondrial antibody test. Chronic viral hepatitis B or C, may also present with lethargy.

In many cases, liver abnormalities can be investigated further in general practice, with the aim of detecting treatable disease. The approach must be tailored to the individual, but after a full history and examination, the next line of tests should include additional blood tests and an ultrasound examination of the liver.

Ultrasound has many advantages as an early investigation for liver dysfunction. It is relatively cheap and free of side-effects, and not only will an ultrasound of the liver detect or exclude pathologies such as space-occupying lesions or biliary obstruction, but it will also give useful information about the size and consistency of the liver, in particular showing the shape of the liver, patency of vessels and the presence of ascites.

Fatty liver
Fatty liver disease is also usually detected on ultrasound, and may be due to either alcohol, or to non-alcoholic fatty liver disease (NAFLD), which has many causes including obesity and the metabolic syndrome, diabetes, hyperlipidaemia and some drugs.

With the increasing prevalence of obesity, NAFLD is now seen more commonly. It is not always benign and in the presence of hepatitis there is a high risk of progression to cirrhosis and the development of liver cancer.

It is very hard to distinguish between alcoholic liver disease, fatty liver or steatohepatitis without a liver biopsy.

Treatment is of the underlying cause of the disease which can be determined using a battery of further tests.

The role of drugs such as metformin or the glitazones in treating liver disease remains to be established.

Blunderbuss approach
At present, it is not clear whether it is more clinically effective and cost-effective to adopt a blunderbuss approach to LFT, measure all analytes and await the results, or to adopt a step-approach looking at those factors that are more likely clinically.

The pattern of abnormalities found in an initial LFT will suggest the most likely cause of disease and this may be used to decide which further tests need to be done. For example, predominantly elevated alkaline phosphatase and bilirubin will indicate a cholestatic process, and predominantly raised transaminases will suggest a hepatitic problem (see box).

However, a modified blunderbuss approach is recommended, since liver diseases commonly co-exist, and two conditions will have a synergistic effect. For example, those with obesity and chronic hepatitis C will have a more progressive course and treating both causes will be beneficial.

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