Synopsis
Recognise a cholestatic biochemical pattern, establish whether alkaline phosphatase is hepatobiliary, integrate urgency and imaging, and pursue extrahepatic and intrahepatic causes without reflexive repeat testing.
- A cholestatic pattern means ALP predominates over ALT; use the laboratory upper limits rather than comparing raw numbers with different reference ranges.
- Confirm a hepatobiliary source with GGT and clinical context because bone disease, growth, pregnancy and healing fractures can raise ALP independently of bile flow.
- Review bilirubin, albumin, INR, full blood count, symptoms, medicines and previous results; the height of an isolated enzyme does not determine urgency by itself.
Key red flags
A dilated bile duct with systemic illness needs urgent assessment for drainage; antibiotics alone do not relieve an obstructed infected system.
Unexplained clinical jaundice or suspected hepatic or biliary malignancy warrants immediate or urgent referral rather than serial community blood tests.
Rising INR, falling glucose, encephalopathy or acute kidney injury shifts attention from enzyme classification to threatened liver and multiorgan function.
Progressive painless jaundice, weight loss and worsening conjugated bilirubin require urgent cancer-focused imaging and referral even if ALP elevation is only moderate.
Reasoning priorities
Define the relationship among bilirubin, ALT, ALP, GGT and albumin rather than interpreting ALP in isolation.
Express ALT and ALP relative to their upper limits; add INR in significant illness because albumin changes slowly and may reflect non-hepatic factors.
Worked reasoning
A 72-year-old with new pruritus and 5 kg weight loss has total bilirubin 116 micromol/L, conjugated bilirubin 101 micromol/L, ALP 612 U/L with upper limit 130, ALT 88 U/L with upper limit 45, GGT 740 U/L and INR 1.1; ultrasound shows dilated intrahepatic and extrahepatic ducts.
- ALP is 612/130 = 4.7 times its upper limit and ALT is 88/45 = 2.0 times its upper limit. This is ALP predominance with a measured predominantly conjugated bilirubin rise; GGT supports a hepatobiliary source.
- Combine the progressive itch, weight loss and dilated ducts: an extrahepatic malignant obstruction is now more concerning than bone ALP or isolated intrahepatic drug injury.
- The patient is afebrile, stable and fit for investigation: obtain urgent pancreatic-protocol CT before elective duct drainage. It shows a 2.8 cm pancreatic-head mass without major-vessel involvement or distant disease. Because CT-localised pancreatic cancer is being considered for treatment, offer staging FDG-PET/CT under NICE NG85; this shows no nodal or distant metastatic focus.
- HPB review confirms resectability and satisfactory cardiopulmonary, nutritional and functional fitness. The patient chooses prompt pancreaticoduodenectomy without a preoperative stent because there is no cholangitis, intolerable symptom burden or treatment delay. Resection histology confirms adenocarcinoma with clear margins; by postoperative day ten bilirubin has fallen to 22 micromol/L and recovery permits an oncology referral.