ABNORMAL LFT PROTOCOL (updated 2013)
Jaundice or elevated
bilirubin?
ALT and Alk phos
Albumin all normal?
Patient ill or
bilirubin > 200?
ADMIT ACUTELY or
DISCUSS (*)
Bilirubin 100-200?
Bilirubin <100?
Elevated alk phos?
Investigate according to
GILBERT PROTOCOL
Phone or fax consultant
gastro for urgent clinic
visit (*)
Check Hep A/B serology,
refer (*)
Normal ALT and GGT?
BONY!
Alk Phos
protocol
ALT > 100




Not ill
Normal alk phos
ALT < 100
Not jaundiced
REFER
GP to investigate according to
TRANSAMINASE
PROTOCOL
(*) When referring jaundiced patients please
provide a detailed drug history (including all
prescriptions issued within the preceding three
months) and also full results of all investigations
performed. On this basis we can decide on
urgency required. Most, but not all, jaundiced
patients will be allocated to urgent appts.
GAMMA GT
GGT is a sensitive marker for hepatobiliary disease, but its use is limited by poor
specificity.
Causes of raised GGT:
 Hepatobiliary disease (often with other liver enzyme abnormalities)
 Pancreatic disease
 Alcoholism
 Chronic obstructive pulmonary disease
 Renal failure
 Diabetes
 Myocardial infarction
 Drugs, e.g. carbamazepine, phenytoin and barbiturates and oral contraceptive pill
The use of GGT is in supporting a hepatobiliary source for other raised liver enzymes,
e.g. ALP.
GILBERT PROTOCOL
Isolated hyperbilirubinaemia
This is usually Gilbert’s syndrome.
Check: LFTs, conjugated v unconjugated bilirubin, haemoglobin, reticulocyte count.
Criteria
 Bilirubin fluctuates but <70. (Some Gilberts patients go yellower than this but they are
probably worth investigating more carefully: REFER or DISCUSS.)
 Bilirubin will be higher if patient fasting or during intercurrent illness.
 Ask for conjugated v. unconjugated bilirubin: the hyperbilirubinaemia should be
largely unconjugated, but don’t trust the laboratory ranges for conjugated bilirubin,
they are too strict, and many Gilberts patients have an elevated conjugated bilirubin.
 Normal FBC and reticulocyte count (to exclude haemolytic anaemia).
If the patient is well and meets all the above criteria, reassure and explain the diagnosis.
Give information leaflet. The patient does not need an ultrasound or referral.
RAISED TRANSAMINASES
Common causes:
 Alcohol
 Viral hepatitis
 Steatosis
 Medications/toxins e.g. NSAIDs, antibiotics, statins, antiepileptics,
antituberculosis drugs
Less Common causes:
 Autoimmune hepatitis
 Haemochromatosis
 Alpha1-antitrypsin deficiency
 Wilson’s disease
Non-hepatic causes of raised ALT (usually small rises, <120 U/L):
 Coeliac disease
 Strenuous exercise
 Muscle disease
 Endocrine disease e.g. Hypo- and hyper-thyroidism
TRANSAMINASE PROTOCOL
Most patients with persistently elevated ALT have fatty liver disease due to
alcohol +/- obesity +/- diabetes +/- hyperlipidaemia
STEP 1
 Careful alcohol history. If intake > 14u/week encourage the patient to abstain
completely.
 Careful drug history. Stop any medications that may be relevant.
 Think about causes of fatty liver: diabetes, obesity, excess alcohol.
... then recheck the LFTs in 3-4 weeks.
STEP 2: If transaminases > 3x normal proceed to Step 2 & 3 invx and refer
If transaminases < 3x normal then …..
 Organise the following bloods & GP review:
 Weigh the patient and calculate BMI. (BMI>25 is abnormal and diseaseassociated.)
 Check BP
 Fasting chol:HDL & Trigs, Fasting Blood Sugar, FBC and Gamma GT
 GP Review 1 week later
If alcohol or fatty infiltration likely then support lifestyle changes and re-check after 3
months.
If not or if the lfts have not resolved after the 3 months of lifestyle changes then
arrange the following investigations and consider referral:
STEP 3:
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

Hep B and Hep C serology
Autoantibodies including AMA, ASMA, ANF
Coeliac screen
Immunoglobulin levels
Ferritin, Alpha-1-antitrypsin
Caeruloplasmin if patient aged under 35y
TFT
INR
If ALT persistently more than twice normal consider liver ultrasound. Note - not
everyone needs an ultrasound!
FATTY LIVER DISEASE
Only consider the diagnosis if ….






HepB, HepC, ferritin, alpha-1-antitrypsin (and caeruloplasmin if age<35) are normal
Negative TTG, ANF, antimitochondrial and smooth muscle antibodies
Normal platelet count and INR
Normal albumin
There is a reasonable cause such as obesity, alcohol, diabetes, hyperlipidaemia
If ultrasound performed, there should be no splenomegaly and the liver should be
either “fatty” (echogenic) or normal
 Transaminases are below 80 and there is no progressive deterioration.
Address risk factors such as alcohol, obesity. Treat any concurrent conditions such as
diabetes and hypertension and hyperlipidaemia. Recheck LFT in 3-4 months. Referral is
not usually necessary except if they are obese, age>45 with NIDDM (as these patients
are at higher risk of NASH and progression to cirrhosis).
Statins are safe to prescribe if the above criteria are satisfied and the patients are
low risk for NASH
ALKALINE PHOSPHATASE PROTOCOL
Reference intervals contain 95% of the population, therefore 2.5% of the normal
population have values above the upper reference limit. The combined analytical and
biological variation for serum ALP is around 8%. For example, an ALP result of 125
U/L could be between 108 U/L and 143 U/L, spanning the upper reference limit. Minor
increases in serum ALP levels are therefore more likely to be analytical, physiological, or
statistical anomalies rather than indicating disease.
Elevations may be physiological or pathological
Common causes for raised ALP:
Physiological
 Third trimester of pregnancy
 Adolescents, due to bone growth
 Benign, familial
Pathological
 Bile duct obstruction
 Primary biliary cirrhosis
 Primary sclerosing cholangitis
 Drug induced cholestasis, e.g. anabolic steroids
 Metastatic liver disease
 Bone disease e.g Pagets
 Heart failure
Isolated raised alk phos with normal ALT and gamma GT
This suggests alk phos of bony origin. A careful medical and drug history and physical
examination. Key features include abdominal pain or swelling, unintentional weight loss,
back pain, bone pain, clinical indicators of liver disease, congestive cardiac failure, and
end stage chronic kidney disease.
If patients are asymptomatic but have raised ALP levels of unknown cause, then the test
for ALP should be repeated with Gamma GT, ALT, adj calcium, (PTH?) and Vit D
levels, TFTs, Cr&Es, and FBC checked within four weeks if not part of the original
profile. Don’t forget PSA in men, CXR in smoker, plasmaphoresis and ESR and breast
exam if malignancy suspected. Also Paget’s Disease in the elderly.
Raised alk phos with abnormal ALT and gamma GT
1. If alk phos rasied check lfts & gamma gt. If abnormal then refer USS, and consider
Antimitochondrial antibodies, Smooth Muscle Antibodies and Immunoglobulins.
2. If alk phos < 1.5 Upper Limit of Normal (ULN) re-check in 1 month. Values up to
20% over ULN are likely to be statistical rather than clinical 'abnormals'.
3. If < 1.2 x ULN recheck at 3 months and annually if stable
4. If on repeat > 1.2 x ULN then arrange alk phos isoenzymes (and if of bony origin
consider PSA in men, CXR in smokers, breast exam in women, FBC & ESR +/myeloma screen etc) but if not of bony origin consider transaminase bloods and
discuss/refer.
5. If alkaline phosphatase >2 ULN (on a single measurement) then further investigation
& probable referral is indicated.
Appendix
Drugs which causes abnormal LFTs
Common drug causes of raised alkaline phosphatase levels 6 17
Drugs
Mechanism
Antibiotics:
Penicillin derivatives
Intrahepatic cholestasis
Erythromycin
Intrahepatic cholestasis
Aminoglycosides
Enzyme induction
Antiepileptic drugs:
Carbamazepine
Intrahepatic cholestasis
Phenobarbital
Enzyme induction
Phenytoin
Enzyme induction
Antihistamines:
Cetirizine
Intrahepatic cholestasis
Cardiovascular drugs:
Captopril
Intrahepatic cholestasis
Diltiazem
Enzyme induction
Felodipine
Enzyme induction
Disease modifying agents:
Penicillamine
Intrahepatic cholestasis
Oral contraceptive pill (oestrogen) Enzyme induction
Steroids
Enzyme induction
Psychotropic drugs:
Monoamine oxidase inhibitors
Intrahepatic cholestasis
Chlorpromazine
Intrahepatic cholestasis
Guideline d erived from the 2002 protocol by Dr G Sobala, Consultant Physician,
Huddersfield Royal Infirmary. Updated using recent BMJ publications & GP notebook
2013.
Useful references
BMJ 2001;322:33-36 ABC of diseases of liver, pancreas, and biliary system
BMJ 2006;333:481-483 (2 September), doi:10.1136/bmj.333.7566.481 Cases in primary care laboratory medicine Biochemical
"liver function tests"
Southern Derbyshire abnormal lfts guideline 2012
BMJ 2013;346:f976 interpretation an isolated raised alkaline phosphatase