What is the next step for a patient with elevated alkaline phosphatase (ALP) level, normal liver enzymes, and normal Computed Tomography (CT) of the abdomen and pelvis?

Next Step: Measure GGT or ALP Isoenzymes to Confirm Source

The next step is to measure gamma-glutamyl transferase (GGT) to confirm whether the elevated ALP is of hepatic or non-hepatic origin. 1

Rationale for GGT Measurement

• GGT measurement is the recommended first step when ALP is elevated with normal liver enzymes (ALT/AST), as it helps differentiate hepatobiliary from bone sources 1
• Elevated GGT confirms hepatobiliary origin and warrants further hepatic workup, while normal GGT suggests bone or other non-hepatic sources 1, 2
• If GGT is unavailable or equivocal, ALP isoenzyme fractionation can determine the percentage derived from liver versus bone 1

If GGT is Elevated (Hepatobiliary Source Confirmed)

Since you already have a normal CT abdomen/pelvis, the diagnostic pathway shifts based on GGT results:

Immediate Actions:

• Obtain a complete liver panel including total and direct bilirubin, albumin, and prothrombin time to assess hepatic synthetic function 2
• Review all medications thoroughly, particularly in older patients, as drug-induced cholestasis comprises up to 61% of cases in patients ≥60 years 1
• Screen for specific risk factors including alcohol intake (>20 g/day in women, >30 g/day in men), viral hepatitis, and inflammatory bowel disease 1

Next Imaging Step:

• Proceed to MRI with MRCP if ALP remains elevated, as this is superior to CT for detecting intrahepatic biliary abnormalities, primary sclerosing cholangitis, and small duct disease 3, 1
• MRI with MRCP is particularly useful for sustained ALP elevation with negative initial imaging, as it can identify choledocholithiasis, biliary strictures, and infiltrative diseases 3

Key Differential Diagnoses to Consider:

• Primary biliary cholangitis or primary sclerosing cholangitis - especially if inflammatory bowel disease is present 3, 1
• Drug-induced cholestasis - review all medications, supplements, and herbal products 1
• Infiltrative diseases including sarcoidosis, amyloidosis, or hepatic metastases 3, 1
• Partial bile duct obstruction not visible on CT 3

If GGT is Normal (Non-Hepatic Source)

• Measure bone-specific alkaline phosphatase (B-ALP) to confirm bone origin 1
• Consider bone disorders including Paget's disease, bony metastases, or fractures 1
• Targeted imaging based on symptoms - bone scan is indicated if there is localized bone pain 1

Important Clinical Pitfalls

• Normal CT does not exclude intrahepatic cholestasis - CT is less sensitive than MRI/MRCP for biliary tree evaluation 3
• Sepsis can cause extremely high ALP with normal bilirubin - consider if patient appears systemically ill 4
• ALP elevation severity matters: Your level of 158 U/L represents mild elevation (<5× upper limit of normal), allowing systematic outpatient evaluation rather than urgent workup 1, 2
• Do not assume non-alcoholic steatohepatitis (NASH) as the cause, as ALP elevation ≥2× ULN is atypical in NASH 1

Follow-Up Strategy

• If initial evaluation is unrevealing, repeat ALP measurement in 1-3 months and monitor closely 1
• Persistent or rising ALP warrants further investigation even if initial workup is negative 1