- Initial investigation for potential liver disease should include bilirubin, albumin, alanine transaminase (ALT), alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT), together with a full blood count if not already performed within the previous 12 months
When should liver blood tests be checked?
- Non-specific symptoms (e.g. fatigue, nausea, or anorexia in autoimmune hepatitis)
- Evidence of chronic liver disease (e.g. cirrhosis, portal hypertension, liver failure)
- Conditions which are associated with a high risk of developing liver disease, such as:
- pre-existing autoimmune disease
- patients with inflammatory bowel disease (including ulcerative colitis and Crohn’s disease)
- Use of hepatotoxic drugs (e.g. carbamezepine, methyldopa, minocycline, macrolide antibiotics)
- Family history of liver diseases (e.g. haemochromatosis, Wilson’s disease)
- Viral hepatitis
- while liver blood tests can give an indication of necro-inflammation or of advanced fibrosis, a key early test is serology for viral hepatitis in high-risk groups as liver blood tests can be normal in this setting (table 1)
- Presence of lifestyle risk factors associated with the development of non-alcoholic fatty liver disease (e.g. obesity, type 2 diabetes)
|Standard liver aetiology panel||Extended liver aetiology panel|
|PCR=polymerase chain reaction; PSC=primary sclerosing cholangitis; LKM=liver kidney miscrosome; ANCA=antineutrophil cytoplasmic antibodies.|
|Viral hepatitis||Hepatitis B surface antigen AND hepatitis C antibody (with follow-on PCR if positive)||Anti-HBc and anti-HBs hepatitis B DNA quantification of hepatitis delta in high-prevalence areas|
|Iron overload||Ferritin AND transferrin saturation||Haemochromatosis gene testing|
|Autoimmune liver disease (excluding PSC)||Anti-mitochondrial antibody, anti-smooth muscle antibody, antinuclear antibody, serum immunoglobulins||Anti-LKM antibody and coeliac antibodies (consider ANCA in the presence of cholestatic liver blood tests)|
|Metabolic liver disease||Alpha-1-antitrypsin level; thyroid function tests; caeruloplasmin (age >3 and <40 years) ± urinary copper collection|
Does the extent and duration of abnormal liver blood tests determine subsequent investigation?
- Abnormal liver blood test results should only be interpreted after review of the previous results, past medical history and current medical condition
- The extent of liver blood test abnormality is not necessarily a guide to clinical significance. This is determined by the specific analyte which is abnormal (outside the reference range) and the clinical context
Duration of abnormality and retesting
- Patients with abnormal liver blood tests should be considered for investigation with a liver aetiology screen irrespective of level and duration of abnormality. Abnormal refers to an analyte which is outside the laboratory reference range
Clinical pattern recognition for liver blood tests
Response to abnormal liver blood tests: outcomes and pathways
- As indicated in figure 1 the presence of unexplained clinical jaundice or suspicion of possible hepatic or biliary malignancy should lead to an immediate referral
- In all other adults with incidentally raised liver enzymes it is important to take a careful history and perform a targeted clinical examination to look for the cause
- In adults a standard liver aetiology screen should include abdominal ultrasound scan (USS), hepatitis B surface antigen, hepatitis C antibody (with follow-on polymerase chain reaction if positive), anti-mitochondrial antibody, anti-smooth muscle antibody, antinuclear antibody, serum immunoglobulins, simultaneous serum ferritin and transferrin saturation
- In children, ferritin and transferrin saturation may not be indicated, but autoantibody panel should include anti-liver kidney microsomal antibody and coeliac antibodies. Alpha-1-antitrypsin level and caeruloplasmin (age >3 years) should be included, and abnormalities discussed with an appropriate inherited metabolic disease specialist
Approach to common conditions
- Adults with NAFLD should undergo risk stratification to determine their extent of liver fibrosis.
- first-line testing should use either FIB-4 or NAFLD Fibrosis Score. Calculation facilities for FIB-4 and NFS should be incorporated in all primary care computer systems.
- second-line testing requires a quantitative assessment of fibrosis with tests such as serum ELF measurements or Fibroscan/ARFI elastography
- hepatologists at a local level should champion this idea and discuss it with commissioners of health to deal with the burden of liver disease in their area (figures 1 and 2)
- Consider referral to alcohol services for all adults with alcohol-related liver disease (ARLD) with evidence of alcohol dependency as defined by an AUDIT score of >19
- Harmful drinkers should undergo risk stratification with clinical assessment and Fibroscan/ARFI elastography. Adults should be referred to secondary care if there is evidence of advanced liver disease (features of cirrhosis or portal hypertension on imaging or from blood tests) and/or Fibroscan reading is >16kPa (if available)
Approach to a patient with abnormal liver blood tests and a negative extended liver aetiology screen
- When the extended liver aetiology screen is negative (table 1), including an abdominal USS, it is important to re-examine the history to exclude potential drug-induced aetiologies, including over-the-counter preparations and any potential recreational/herbal drug use
- Adults with abnormal liver blood tests, even with a negative extended liver aetiology screen and no risk factors for NAFLD, should be referred/discussed to a gastroenterologist with an interest in liver disease/hepatologist for further evaluation (figure 1)
Want to learn more about this guideline?
Read the related Guidelines in Practice article
full guideline available from…
Newsome P, Cramb R, Davison S et al. Guidelines on the management of abnormal liver blood tests. Gut 2018; 67 (1): 6–19.
First included: March 2018.