Abnormal Liver Function Test (LFT)

Discuss abnormal LFT’s?

  • Liver function tests forms part of the investigative pathway for patients presenting with a wide range of symptoms.
  • The range of normal laboratory values for serum biochemical tests is defined as the mean of the distribution +/- 2 standard deviations of a presumably representative healthy population. By definition, 2.5% of healthy individuals will therefore have an abnormal elevation of a given liver chemistry test. In fact, the National Health and Nutrition Examination Survey 1999-2002 reported the prevalence of elevated ALT was 8.9% in the general population. Thus a significant proportion of the population have abnormal LFTs
  • Fluctuation in ALT levels is recognized and LFT’s should be retested after an interval. If the transaminases normalise, it can probably be ignored.

Discuss the evaluation of abnormal LFTs?

  • Abnormal LFTs should be evaluated in the clinical context of a given patient. The initial evaluation includes:
  • Detailed history
    • Alcohol history
    • H/o previous blood transfusion (esp. prior to 1991)
    • H/o intravenous drug abuse
    • Sexual history
    • Medication history including over the counter medications, herbs etc
    • Family h/o liver disease
  • Physical examination to look for any signs of chronic liver disease
  • If the above enquiry indicates a particular diagnosis, subsequent evaluation is directed toward establishing the diagnosis. However, very often the patient is asymptomatic and there are no diagnostic clues. In such cases, common hepatic diseases should be excluded with non-invasive serologic tests and ultrasound of the liver.
  • Investigations

In those with persistently (>6 months) abnormal LFTs, screening with ultrasound scan, hepatitis B and C serology, Ferritin, TIBC, autoantibodies, immunoglobulin’s and coeliac serology plus screening for alpha-1-antitrypsin deficiency and Wilson’s disease in selected patients will often yield a diagnosis.
Blood glucose, thyroid function tests and lipid profile is also checked.

Discuss the management of persistently abnormal LFTs and negative results of the tests above?

If LFTs are markedly abnormal (transaminases > 5 times abnormal), or if significant symptoms or evidence of chronic or decompensated liver disease are present, then a liver biopsy is usually indicated.

In the absence of above, check for risk factors for NAFLD (BMI, diabetes). If risk factors present are present, they should be addressed and LFTs reassessed at 6 months. If ALT is improving, life style measures should be continued. If ALT fails to improve or if risk factors for NAFLD are absent, a liver biopsy should be considered.

Discuss the aetiology of abnormal LFTs in the presence of negative serological investigations?

In the setting of abnormal liver enzymes in the absence of diagnostic serology, a liver biopsy in a large study (1) of 354 patients showed the following:

NAFLD (including NASH) – 66%
Normal- 06%
Cryptogenic hepatitis-9%
Drug reaction-8%,
Alcohol- 3%,
Others- 7%.

26% of the patients had fibrotic liver disease and 6% cirrhosis. Further, management was altered directly by the liver histology findings in 18%.

Discuss the role of liver biopsy in the setting of abnormal LFTs and negative serology?

Liver biopsy is often recommended in patients with ‘unexplained’ abnormal LFTs in order to determine the cause, to stage hepatic fibrosis and to grade hepatic inflammation. While the information derived from a liver biopsy is useful, performing a liver biopsy on all persons with unexplained abnormal LFTs may not be feasible since this laboratory abnormality is so common. Non invasive methods need to be developed that can evaluate disease severity and likelihood of disease progression in persons with raised aminotransferase activity.
Serum markers, and serum panel markers for the assessment of chronic liver disease, such as Enhanced (European) Liver Fibrosis (ELFTM) test and FibroTest, have been proposed. Liver stiffness measurement using transient elastography (TE) (FibroScan®) is another recently developed technique designed for the assessment of liver fibrosis. These non invasive methods may help us in better defining the extent of the problem in future, however they are not ready for prime time use yet
Thus, the need for liver biopsy should be individualised.


  1. Skelly MM, James PD, Ryder SD. Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology. J Hepatol 2001; 35(2):195–9.
  2. American Gastroenterological Association Medical Position Statement: Evaluation of Liver Chemistry Tests

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