Primary Sclerosing Cholangitis: Paediatric Perspective

About 60% of children are symptomatic at diagnosis [3]. In children, fatigue, pruritus, abdominal pain, steatorrhoea, nutrient deficiencies, weight loss, osteopenia and delayed growth can be seen [1]. Although advanced fibrosis or cirrhosis is observed in up to 40% of children with PSC at the time of diagnosis, only about 5% initially present with complications of portal hypertension [3]. Despite this, evidence of portal hypertension develops in an estimated 40% of children by ten years after diagnosis [4, 5].

Around 70% of individuals with PSC have or subsequently develop colonic IBD, while the estimated prevalence of PSC in IBD patients is ~5% [1, 6]. The true prevalence may be higher, however, given that patients with IBD do not typically undergo routine cholangiography, may not have significant hepatic laboratory test abnormalities and may not undergo routine screening of gamma-glutamyl transferase (GGT). IBD is more often diagnosed before PSC, although the diagnoses can be concurrent and PSC presents first in 25% of patients [1]. Key distinguishing features of the PSC–IBD phenotype are increased risk of active endoscopic and histological disease in the absence of symptoms, pancolitis with severe inflammation in the right colon, rectal sparing and possibly backwash ileitis, as well as a threefold increased risk of colorectal dysplasia.

Bilirubin is normal at diagnosis in the majority of patients with PSC [1]. In adults, elevated serum alkaline phosphatase (ALP) is the most common presenting laboratory test abnormality. In children, however, ALP may be elevated due to non-hepatic causes, such as bone turnover and normal growth, and it is thus less useful in paediatrics [5]. Furthermore, in up to 40% of children with PSC, ALP will be within the normal range. For these reasons, GGT is felt to be a more accurate marker of PSC in children [5]. A paediatric-specific prognostic risk index [Sclerosing Cholangitis Outcomes in Paediatrics (SCOPE) index] containing total bilirubin, albumin, platelet count, GGT, and cholangiography has recently been created to predict a primary outcome of liver transplantation or death [7]. Given the increased prevalence of autoimmune hepatitis (AIH) in children compared with adults, the American Association for the Study of Liver Diseases (AASLD) 2010 guidelines recommended the use of liver biopsy to assess for AIH in children with PSC [8].

Treatment of PSC is currently inadequate. At the appropriate dosing, ursodeoxycholic acid (UDCA) and oral vancomycin (OVT) have been found to be safe for short-term use and have been associated with biochemical improvement in some patients over time [1]. However, many patients also show spontaneous improvement in liver indices without treatment, and there is no evidence that biochemical improvement prevents or alters the natural history of PSC progression. In a follow-up paediatric study [9], patients who received UDCA or OVT had lower median GGT at six months than those in the untreated group, although there was no significant difference at one year. In those with follow-up biopsies, changes in liver fibrosis were no different between the groups. Finally, there was no significant difference in five-year probability of being listed for liver transplant. In a small, prospective, non-controlled trial [10], children with PSC-IBD were treated with OVT.  All patients had statistically significant reductions in laboratory test values and subjective improvement in symptoms. Stopping OVT during intermittent dosing practices was shown to lead to increased GGT and ALT and worsening of clinical symptoms, which all improved upon re-introduction of medication.  

Current therapies are based on a variety of potential mechanisms but in general are applied across all patients with the disease, without regard to specific mechanisms in individual patients. Paediatric studies will be particularly insightful for all patients with PSC given the lack of co-morbidities and other confounding variables relative to adults.

References

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