Investigations

  • 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 (for example, fatigue, nausea, or anorexia in autoimmune hepatitis)
  • Evidence of chronic liver disease (for example, 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 (for example, carbamezepine, methyldopa, minocycline, macrolide antibiotics)
  • Family history of liver diseases (for example, 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 (for example, obesity, type 2 diabetes).
Table 1: Liver aetiology table for patients with non-acute abnormal liver blood tests
 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

Figure 1: Response to abnormal liver blood tests

BSG NAFLD Figure 1 v2

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

NAFLD

Figure 2: Non-alcoholic fatty liver fibrosis

BSG NAFLD Figure 2

  • 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).

ARLD

Figure 3: Alcohol-related liver disease

Guidelines on the management of abnormal liver blood tests Figure 3

  • 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 >16 kPa (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?

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Read the related Guidelines in Practice article

Full guideline:

https://www.bsg.org.uk/resource/guidelines-on-the-management-of-abnormal-liver-blood-tests.html

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.

Credit:

Lead image: James Thew/stock.adobe.com