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Over the past 40 years mortality from liver disease has increased by 400% across the UK, substantially higher than other countries in Western Europe. Liver disease now represents the third commonest cause of premature death in the UK and has increased exponentially compared with other diseases. The main contributors to liver disease are alcohol, obesity and viral hepatitis. These are largely preventable risk factors that can be targeted with advice and intervention in primary care.
Liver function tests (LFTs) are increasingly checked in primary care and abnormal LFTs are an increasingly common finding. This guideline makes recommendations for the diagnosis and management of abnormal LFTs in adults over 16 years old with little or no symptoms.
This guideline does not apply to children under 16 years of age.
Isolated raised bilirubin - see Figure 1
# If not available use Formula: Unconjugated Bilirubin = Total bilirubin minus (-) conjugated bilirubin level
Isolated cholestatic liver enzymes - see Figure 2
Hepatitic pattern - see Figure 3
1. Obtain a thorough clinical history
NOTE: The majority of adults with abnormal LFTs will be identified to have non-alcohol fatty liver disease (NAFLD) or alcohol-related liver disease (ARLD). Most will not need a referral to hepatology services but will require reinforcement of lifestyle advice and ongoing assessment in primary care
2. Provide general advice as appropriate
3. Review medications – Recent statins *, antibiotics, NSAIDs; STOP any drugs known to be associated with drug-induced liver injury. If there is a temporal relationship between a new medication and LFT changes, consider drug-induced liver injury and consider stopping the drug. Repeat LFTs after 1-3 months.
* Whilst statins can cause an acute change in liver enzymes, they are safe in patients with known chronic liver disease.
4. Refer to liver clinic for advice if certain drugs are more difficult to stop (e.g. neuroleptics, anti-epileptics)
5. Repeat the LFTS – requesting AST (+/- GGT) with a FBC
aAUDIT-C: Alcohol use disorders Identification test consumption: Online link:
bFAST: Fast alcohol screening test: Online link:
When to repeat the LFTs and further action:
|Liver blood test abnormality||When to repeat?||Action|
|Isolated raised bilirubin||When convenient||Fasting LFTs sample with FBC|
|Isolated raised ALP||4 weeks||
Repeat LFTs with GGT
If GGT normal – check vitamin D, bone profile and phosphate level for bone cause (e.g. Vitamin D deficiency, Paget's); exclude pregnancy
If GGT greater than upper limit of normal (ULN), see Step 3: non-invasive liver (NILS), abdominal ultrasound (USS)
If ALT lower than 3x ULN
If ALT greater than 3x ULN
With AST and FBC
With AST and FBC
If ALT remains abnormal, see STEP 3: NILS, USS
|Isolated GGT||Repeat in 1 - 3 months||
Review for significant alcohol consumption, drug history (mainly anti-epileptics), uncontrolled diabetes mellitus (check glycated haemoglobin [HbA1c]), obesity.
If still elevated, check LFTs and consider liver USS.
|Raised Bilirubin with raised ALT or ALP ( see Figure 1)||Urgent referral|
|Red Flags (see Red Flags section)||Urgent referral|
If the abnormalities have persisted for 1-3 months despite the above measures, then a non-invasive liver screen (NILS) should be done:
Based on the history and results, the following pathologies will need referral for further assessment and management:
|Hepititis C infection (HCV)||
HCV antibody positive – check hepatitis C PCR
If positive - refer to hepatology
If negative, repeat 3 months later and if still negative, reassure patient infection has cleared, no need to refer
|Hepatitis B infection (HBV)||HbsAg positive - refer|
|Autoimmune hepatitis (AIH)||ALT increased, positive autoantibodies (SMA, ANA, or LKM) +/- raised IgG; there may be a history of autoimmune diseases|
|Primary biliary cholangitis (PBC)||Raised ALP (Cholestatic pattern), positive antimitochondrial antibody (AMA)|
|Primary sclerosing cholangitis (PSC)||History of inflammatory bowel disease, cholestatic pattern of LFTs|
|Haemochromatosis||Raised ferritin and transferrin saturation (lower than 45%); there might be a history of diabetes and joint pain; Suggest REPEAT test (ensure patient is fasted) and if results are still similar, send genetic screen for Haemochromatosis and refer to Hepatology|
|Wilson's disease||Abnormal low caeruloplasmin performed in a patient below age 55 years old - refer|
|Alpha - 1 - antitrypsin deficiency||Low alpha - 1 antitrypsin (lower than 0.9g/L) - refer|
|SIGNIFICANT FINDING: Any biliary duct dilation on USS||Needs further assessment and URGENT hospital referral|
Patients who do not require referral to liver clinic:
Non-alcohol fatty liver disease (NAFLD) without fibrosis [see Management Step 5 of this guidance] – USS showing fatty liver only, negative liver screen, absence of excessive alcohol consumption, raised BMI or waist circumference, hypertension, impaired fasting glucose or diabetes mellitus type 2, raised triglyceride and low HDL cholesterol. LFT shows mainly isolated raised ALT.
NAFLD is closely associated with the metabolic syndrome and encompasses simple steatosis (fat but no inflammation or hepatocellular injury) through to non-alcoholic steatohepatitis (NASH = fat + inflammation + hepatocellular injury) and fibrosis to cirrhosis. Up to a third of the population has been estimated to have NAFLD and 40% of patients with NAFLD develop progressive fibrosis which can progress to cirrhosis in 10-20%. Patients with cirrhosis are at risk of serious life-threatening complications such as hepatocellular carcinoma, portal hypertension and liver failure.
The most important predictor of mortality in individuals with NAFLD is the stage of liver fibrosis. Patients with moderate or severe liver fibrosis are at an increased risk of mortality and liver related complications in the future. There are several non-invasive scoring systems for fibrosis that have been assessed and validated in NAFLD. These utilise simple blood tests and clinical parameters that can accurately exclude advanced fibrosis. These can be used to risk-stratify patients to decide who requires referral to secondary care for further investigation and management.
The Fibrosis-4 (FIB-4) and NAFLD fibrosis score (NFS) are well-validated for this purpose. We would recommend the FIB-4 score as it performed slightly better than the NFS in most studies and requires fewer variables to calculate.
For all patients with a clinical diagnosis of NAFLD who have had other causes of liver disease excluded, the FIB-4 score should be calculated.
To calculate the FIB-4 score, you need:
Please use the available online calculator:
Presently, the mainstay of treatment for patients with NAFLD without advanced fibrosis is lifestyle modification (weight loss, diet, exercise) and optimisation of diabetes and cardiovascular risk factors.
1. Lose weight if BMI greater than 25 or raised waist circumference
2. Optimise control of diabetes
3. Treat hypertension
4. Advise patients to drink alcohol within national recommended limits. There is no evidence at present to recommend abstinence
5. Assess cardiovascular risk annually – QRISK3 ,consider statin
6. Calculate FIB-4 score every 3 years and refer if FIB-4 score increases above the age-related cut-off
Refer to Hepatology: See the management: Step 4 & 5 in this guideline and Red Flags section of this guidance
Refer to gastroenterology if:
Consider Referral to haematology if:
Referral to Hepatology
Referral to Gastroenterology
Referral to Haematology
Any queries call Dr John Christie 01392 402791, Dr Lin Lee Wong 01392 404615, Dr Ben Hudson 01392 408 808 or Gastro Registrar via switch board 01392 411611
1. Williams R et al; The Lancet Commission: Addressing liver disease in the UK: a blueprint for attaining excellence in health care and reducing premature mortality from lifestyle issues of excess consumption of alcohol, obesity, and viral hepatitis; Lancet 2014; 384: 1953- 1997
2. Sheridan D; Assessment of Abnormal Liver Function Tests; South and West Devon Formulary and Referral 2016 Online access
3. Hudson M, McPherson S et al; Guidelines for the Management of Adults with Asymptomatic Liver Function Abnormalities; Northern England Strategic Clinical Networks; 2016 (version 2)
4. Newsome P et al; Guidelines on the management of abnormal liver blood tests; Gut 2017; 0: 1-14
5. Kwo P et al; American College of Gastroenterology Clinical Guideline: Evaluation of Abnormal Liver
Chemistries; AJG 2017; 122: 18-35
6. Rashid L et al; Southern Derbyshire Shared Care Pathology Guidelines: Abnormal Liver Function Tests (LFTs) in Adults; 2016 Online access:
7. Miller M et al; Development and validation of diagnostic triage criteria for liver disease from a minimum data set enabling the 'intelligent LFT' pathway for the automated assessment of deranged liver enzymes; Frontline Gastroenterology 2018; 9: 175-182
8. EASL-EASD-EASO Clinical Practice Guidelines for the Management of Non-Alcohol Fatty Liver Disease; Journal of Hepatology 2016; 64: 1388-402
9. Gallacher J and Mcpherson S; Practical Diagnosis and Staging of Nonalcoholic Fatty Liver Disease: A Narrative Review; European Medical Journal 2018; 3: 108-118
10. NICE guidance 49: Non-alcohol fatty liver disease (NAFLD): Assessment and management; NICE 2016 Online access
This guideline has been signed off on behalf of NHS Devon CCG
Publication date: November 2019