Assessment of Abnormal Liver Function Tests


Liver disease is the third commonest cause of premature death in people of working age, and, unlike every other major disease, is on the increase.

Mortality rates from liver disease are substantially higher in the UK than other countries in Western Europe.

Alcohol, obesity and viral hepatitis are the main contributors to liver disease and are largely preventable risk factors, amenable to advice and intervention in primary care.

Asymptomatic patients over 16 years old with abnormal liver function tests.

Please note pre-referral criteria are applicable to this guideline and referrals may be returned if this information is not contained within the referral letter. See below.


Signs and Symptoms

  • Moderately raised isolated bilirubin (under 50umol/L) – commonly due to Gilbert's syndrome (or haemolysis) which occurs in 5% of the population, is benign and does not need referral. Check conjugated / unconjugated split to check the rise is unconjugated and exclude haemolysis (reticulocyte count, LDH, haptoglobins)
  • Cholestatic pattern – alkaline phosphatase (ALP) raised significantly more than alanine transaminase (ALT). Consider bone causes of raised ALP (e.g. Paget's), raised gamma-glutamyl transpeptidase (GGT) can help confirm a liver cause
  • Hepatitic pattern - raised ALT (and / or aspartate aminotransferase (AST), although ALP may also be raised

History and Examination

  • Drugs, including herbal remedies
  • Alcohol (see toolkit for AUDIT tool)
  • Recreational drug use
  • Features of metabolic syndrome (see toolkit)
  • Ethnicity
  • Foreign travel

Differential Diagnoses

  • Alcoholic liver disease – Indicators: history, raised mean corpuscular volume (MCV) and GGT, raised immunoglobulin A (IgA), fatty liver on ultrasound scanning, and the AST:ALT >2:1
  • Non-alcoholic fatty liver disease – Indicators: fatty liver on USS, negative liver screen, raised BMI or waist circumference, hypertension, impaired fasting glucose or type 2 diabetes, raised triglycerides, low high-density lipoproteins (HDL) cholesterol, raised IgA. LFT shows mainly isolated raised ALT
  • Chronic Viral Hepatitis – Indicators: risk behaviours, origin from endemic countries, blood transfusion, positive serological markers
  • Primary Biliary Cirrhosis – Indicators: raised ALP (cholestatic), positive anti-mitochondrial antibodies (AMA), raised IgM, history of auto immune (thyroid) disease, fatigue and or itch may be present
  • Primary Sclerosing Cholangitis – Indicators: raised ALP (cholestatic), history of inflammatory bowel disease
  • Auto-immune hepatitis – Indicators: positive antinuclear antibody (ANA) or smooth muscle antibodies (SMA), raised Immunoglobulin G (IgG)
  • Haemochromatosis – Indicators: raised ferritin and transferrin saturations, diabetes, joint pains
  • Wilson's disease request for copper and caeruloplasmin

Red Flags

  • Symptomatic patients with overt jaundice - bilirubin above 50 - refer via fast track jaundice clinic pathway, see Fast-track Jaundice Clinical Referral Guideline
  • Patients with upper abdominal pain and/ or weight loss - consider referral via 2ww upper GI pathway
  • Other signs of liver decompensation - ascites, encephalopathy, bleeding - for assessment either as an urgent admission via Medical Assessment Unit (AMU) or refer for urgent outpatient appointment
  • ALT over 10 times upper normal limit (ULN) - Please telephone on-call Hepatologist at Derriford Hospital for advice


Most recent
  • AST and ALT
  • ALP
  • Bilirubin (Bili)
  • Albumin (Alb)
  • GGT
  • Full Blood Count (FBC)
Within 1 year
  • IgA
  • IgG
  • Immunoglobulin M (IgM)
  • Antinuclear Antibody (ANA)
  • Smooth Muscle (SMA)
  • AMA
Within 5 years
  • Ferritin
  • Transferrin Saturation
  • Hepatitis B surface antigen
  • Hepatitis C antibody

Ultrasound scan of liver, biliary tree and pancreas


ALT 40-80
  • AUDIT C to stage alcohol risk
  • reduce alcohol intake - encourage abstinence
  • if BMI over 25 encourage weight loss
  • review recently started medications e.g. statins, antibiotics
  • assess viral hepatitis risk
  • re-check with AST in 3 months if suspected non-alcoholic fatty liver disease (NAFLD) or alcoholic liver disease
ALT over 80
  • As above but recheck in 4 weeks with AST
ALP over upper limit of normal
  • recheck in 4 weeks with GGT
  • if GGT is normal then check bone profile and phosphate to assess for a bone cause such as Pagets or vitamin D deficiency
Isolated raised GGT
  1. alcohol- measure MCV and AST:ALT >2:1
  2. drugs history - mainly anti-epileptics
  3. uncontrolled Diabetes Mellitus (DM)- check HbA1c
  4. obesity

When the liver enzymes are rechecked if:

  • ALT remains abnormal
  • ALP greater than the upper limit of normal with GGT greater than the upper limit of normal

Then perform:

  • Chronic liver disease screen (In Order Sets on ICE) including AST
  • Liver ultrasound scan


Referral Criteria

  • All of the investigations as per ICE and a liver ultrasound results must be included
  • The management must have followed the above pathway

Without these, the referral will be returned

With them, stratification will be possible through Rapid Referral Review (RRR) by the Hepatology team who will then manage appropriately

Referral Instructions

  • Refer using the e-Referral Service:
    • Specialty: GI & Liver (medical and surgical)
    • Clinic type: Hepatology
    • Service: DRSS-Western-Hepatology-Consultant Review-Devon CCG-15N

Referral Forms

DRSS Referral Proforma

Supporting Information

Patient Information – Liver Function Tests patient leaflet


British Society of Gastroenterology

British Liver Trust web site

Pathway Group

This pathway has been signed off on behalf of the NEW Devon CCG Western locality.

David Sheridan - Consultant Hepatologist

Publication date: 23 May 2016


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