From the Guidelines
Persistently elevated alkaline phosphatase (ALP) levels in a patient with ascending cholangitis and decreasing white blood cell (WBC) count, following a negative endoscopic retrograde cholangiopancreatography (ERCP) and sphincterectomy, are most likely due to underlying biliary pathology such as primary sclerosing cholangitis (PSC), incomplete biliary drainage, or strictures. The patient's clinical presentation and laboratory findings, including elevated ALP levels, suggest ongoing biliary obstruction or inflammation, despite improvement in WBC count after sphincterotomy 1. The most recent and highest quality study recommends the use of magnetic resonance cholangiopancreaticography (MRCP) as the preferred diagnostic test for PSC, with a pooled sensitivity and specificity of 86% and 94%, respectively 1.
Diagnostic Approach
- Repeat imaging with MRCP or endoscopic ultrasound to identify any missed pathology, such as strictures or stones, is essential in this patient.
- If a mechanical obstruction is found, repeat ERCP should be considered to relieve the obstruction.
- Biliary stent placement may be necessary if a stricture is identified.
Management
- While awaiting definitive diagnosis, starting ursodeoxycholic acid 13-15 mg/kg/day in divided doses to improve bile flow is recommended 1.
- Empiric antibiotics, such as piperacillin-tazobactam 3.375g IV q6h or ciprofloxacin 500mg PO BID plus metronidazole 500mg PO TID, should be continued for 7-10 days total to cover potential bacterial infection.
- If no mechanical obstruction is found, consider liver biopsy to evaluate for primary sclerosing cholangitis, drug-induced liver injury, or other hepatic pathologies 1.
Rationale
The rising ALP despite clinical improvement suggests that while the acute infection may be resolving, the underlying biliary pathology remains untreated, necessitating further investigation to identify and address the root cause 1. Primary sclerosing cholangitis is a chronic bile duct disease that can cause persistent elevation of ALP levels, and its diagnosis should be considered in patients with elevated serum markers of cholestasis of unknown cause, normal high-quality cholangiography, and compatible histology of PSC 1.
From the Research
Possible Causes of Elevated Alkaline Phosphatase (ALK) Levels
- The patient's condition of ascending cholangitis, despite a negative endoscopic retrograde cholangiopancreatography (ERCP) and sphincterectomy, may still be associated with elevated ALK levels due to ongoing biliary obstruction or infection 2.
- Cholestatic liver disease, which is characterized by an increase in ALK levels, can be caused by various factors, including biliary strictures or stones, and may not always be accompanied by a significant increase in transaminases 3, 4.
- An isolated elevated ALK level can be associated with underlying malignancy, bone disease, or other disorders, and may not always be related to liver disease 5.
- Primary sclerosing cholangitis, a condition that can cause cholestasis and elevated ALK levels, may exist in an occult state without symptoms or increase in serum ALK activity, and a normal ALK level does not preclude further investigation for this condition 6.
Clinical Implications
- The patient's decreasing white blood cell (WBC) count may indicate a response to treatment, but the persistently elevated ALK levels suggest that the underlying cause of the cholangitis has not been fully resolved 2.
- Further investigation, including imaging studies and liver function tests, may be necessary to determine the cause of the elevated ALK levels and to guide further treatment 3, 4.
- The patient's clinical presentation and laboratory results should be carefully evaluated to determine the likelihood of underlying malignancy or other conditions that may be associated with elevated ALK levels 5.