Budesonide/ursodesoxycholic acid in sclerosing cholangitis of critical illness

Introduction: Recent advances in ICU care have improved survival in critically ill patients. This development has given rise to formerly unknown complications involving the biliary system. Sclerosing cholangitis in critically ill patients (SC-CIP) may develop after sepsis/shock and can rapidly progress to biliary cirrhosis. So far, ursodesoxycholic acid (UDCA) is the only recommended pharmacological therapy, but efficacy is limited. Budesonide, a topically acting oral corticosteroid with extensive first pass hepatic metabolism, could represent a potential therapeutic alternative for SC-CIP.

Patients and methods: We studied 7 consecutive patients with SC-CIP. Diagnosis was made by MRCP followed by ERCP (n=4), biopsy (n=4), or clinically (n=2). All patients were treated with UDCA (≥10mg/kg/day); infected patients received antibiotics. Budesonide was commenced at 9mg/day and gradually tapered to 6 or 3mg/day, with the longest treatment lasting for over 2yrs. Obstructive casts and new strictures requiring treatment were detected by ERCP but not routine ultrasound as late as 14 months after diagnosis. One patient (#6) progressed to cirrhosis with secondary adrenal insufficiency, another (#5) developed insulin-dependent diabetes.

Results:

Patient	cause	AP-GGT-Bil((BR))(U/I-U/I-mg/dl)((BR))before treatment	AP-GGT-Bil((BR))(U/I-U/I-mg/dl)((BR))after treatment	clinical outcome
#1	CABG	414–470-n.a.	182–284–0,83	resolved
#2	NSTEMI	758–761–33,6	480–566–19,9	partial response
#3	CPR	328–461–0,46	107–77–0,46	resolved
#4	CABG/AVR	659–1289–2,13	255–535–0,97	resolved
#5	CABG/AVR	995–1021–4,11	2032–1586–19,6	no response
#6	Sepsis	858–458–0,41	136–152–0,43	resolved
#7	Trauma	311–142–1,91	90–18–0,75	resolved

Discussion: In this pilot study, budesonide/UDCA treatment was clinically effective in 6/7 patients with SC-CIP; side effects occurred in 2/7. Budesonide deserves further investigation as potential treatment for SC-CIP.

Reference: Rümmele, P et al. Nat Rev Gastroenterol Hepatol 2009;6:287–95