Ursodeoxycholic Acid in Pediatric Primary Sclerosing Cholangitis

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A large retrospective study (M Deneau, M Perito, A Ricciuto, N Gupta et al. J Pediatr 2019; 209: 92-6) examined the outcomes/response of ursodeoxycholic acid (UDCA) for pediatric primary sclerosing cholangitis (PSC).

Background:

  • “Within 10 years of diagnosis, 30% of children with PSC will require liver transplantation and 50% of children will develop complications, including biliary strictures and hypertension.”
  • Because UDCA has not been shown to improve survival (& may worsen outcomes), it is not recommended in adults by the AASLD.
  • In pediatrics, UDCA remains the most common treatment, used in more that 80% on long-term treatment

Study population/methods:

  • 263 patients at 46 centers
  • Median age 12.1 years
  • UDCA median dose: 15 mg/kg/day

Key findings:

  • Normalization of GGT (<50 IU/L) occurred in 46% of patients in the first year after diagnosis
  • Patients with normalization was less likely among patients with Crohn’s disease and those with laboratory profiles indicative of more advanced hepatobiliary fibrosis (eg. lower platelet count, lower albumin, hyperbilirubinemia)
  • The 5-year survival with native liver was 99% in those who achieved normalization vs 77% in those who did not
  • Even in those without normalization, improvement in GGT was associated with better outcomes. “Those who had a reduction in GGT of >75% had nearly the same long-term survival as those with GGT<50 IU/L at 1 year.”
  • It has previously been shown that nearly “one-third of children who are UDCA-naive have spontaneous GGT normalization by 1 year.”  Thus, the number to treat with UDCA to have one additional case of GGT normalization is four.
  • In a previous study, one-third of patients with GGT normalization on UDCA therapy for 1 year, maintained GGT <29 after withdrawal of UDCA for 12 weeks.

The authors note that “patients who do not achieve normalization could reasonably stop UDCA as they are likely not receiving clinical benefit.”

My take: This study shows that patients who have improvement/normalization of GGT with UDCA therapy have improved outcomes.  The retrospective design of the study limits conclusions about whether UDCA therapy actually improves long-term outcomes, particularly since UDCA at higher doses has been associated with detrimental affects in adults with PSC.

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Pablo Picasso, Le Compotier (Fruit Bowl) at Sofia Reina
https://www.museoreinasofia.es/en/collection/artwork/compotier-fruit-bowl

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.