Abnormal Liver Function Tests

Abnormal Liver Function Tests

Abnormal Liver Function Tests (LFTs) – what to do?


 Somerset Abnormal LFT Algorithm- click here to view


If the patient is unwell +/- pyrexia (e.g. sepsis), urgent clinical attention is required as some patient may benefit from acute admission into hospital (if working with sewage, consider leptospirosis).

For patients with likely ‘acute hepatitis’ (high ALT plus non-specific illness), check the following: Hep A, Hep B, EBV, CMV, +/- Hep E if other results negative (‘acute hepatitis screen’ on lab testing). Add Hep C if high-risk behaviour (e.g. intravenous drug use; men who have sex with men).

The British Society of Gastroenterology (BSG) has published its “Guidelines on the management of abnormal liver blood tests” in 2017 (Newsome PN, et al. Gut 2017), for more information.

  • Mildly abnormal liver test results are a common and often incidental finding. In the absence of jaundice or symptoms suggestive of biliary or hepatic disease, mild to moderate elevation in the ALT (40–200) or the ALP (110–500) usually requires investigation, normally only on a routine basis. The ALT reflects hepatocellular injury, whilst the ALP often reflects biliary or obstructive liver disease. However, there is a considerable overlap in the degree of elevation of both these enzymes in both intrinsic and obstructive liver disease. An isolated raised ALP might not be of liver origin (e.g. bone, small intestine), particularly in the context of a normal gamma-GT (not liver-specific). Functional liver assessment is best done by looking at bilirubin (high), albumin (low) and INR (high), as well as platelet count (low); ALT and ALP reflect liver cell injury.
  • In young patients with persistently abnormal LFTs check serum copper & caerulo­plasmin, and in acute presentation consider Hep A, Hep B, Hep E, EBV, CMV serology (Hep C in patients with high-risk behaviour).
  • The commonest causes of abnormal liver function tests (LFTs) are, in no particular order:
    • ‘Fatty liver’ (NAFLD, non-alcoholic fatty liver disease) – spectrum from echo-bright US abnormality over NASH (non-alcoholic steato-hepatitis) to NAFLD-related liver cirrhosis
    • Alcohol (alcohol-related liver disease, ARLD)
    • Drugs or medication (drug-induced liver injury = DILI)
    • Chronic viral hepatitis (B and/or C)
    • Obstructive biliary disease, e.g. gallstones or malignancy
    • Infiltrative diseases of the liver (e.g. neoplasia)
    • Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC)  
    • Non-invasive liver screen (NILS) investigations reveal a cause for liver test abnormalities in approximately 80–90% of patients. In this remaining 10 to 20% of patients, we then need to decide whether these patients should undergo further investigations like non-invasive fibrosis blood tests (e.g. Fib-4, NAFLD fibrosis, ELF score) or ultrasound-based elasticity assessment (e.g. FibroScan®, 'stiffness') or liver biopsy (histology). Many specialists will perform some of those investigations when there is persistent (more than six months) elevation of ALT levels.  However, if there is strong reason to believe that the abnormal LFTs are due to alcohol or ‘fatty liver’ (NAFLD), patients should attempt a period of alcohol abstinence or weight loss (ideally, 5-10%) to assess whether there is any improvement in the LFT results before a more invasive investigation is performed. Previous studies have shown that in this group of patients the diagnoses made after liver biopsy tends to be as follows: approx. 1/3 non-alcoholic steato-hepatitis (NASH; i.e. risk of fibrosis progression), 1/3 simple ‘fatty liver’; less than 1/10 had cryptogenic hepatitis (9%) and drug-related liver injury (8%); only 2% had autoimmune hepatitis (Skelly M, et al. J Hepatol. 2001; analysing 354 patients’ liver biopsy specimens).