The Sclerosing Cholangitis Outcomes in Pediatrics (SCOPE) Index: A Prognostic Tool for Children

Abstract

Background and Aims Disease progression in children with primary sclerosing cholangitis (PSC) is variable. Prognostic and risk‐stratification tools exist for adult‐onset PSC, but not for children. We aimed to create a tool that accounts for the biochemical and phenotypic features and early disease stage of pediatric PSC. Approach and Results We used retrospective data from the Pediatric PSC Consortium. The training cohort contained 1,012 patients from 40 centers. We generated a multivariate risk index (Sclerosing Cholangitis Outcomes in Pediatrics [SCOPE] index) that contained total bilirubin, albumin, platelet count, gamma glutamyltransferase, and cholangiography to predict a primary outcome of liver transplantation or death (TD) and a broader secondary outcome that included portal hypertensive, biliary, and cancer complications termed hepatobiliary complications (HBCs). The model stratified patients as low, medium, or high risk based on progression to TD at rates of <1%, 3%, and 9% annually and to HBCs at rates of 2%, 6%, and 13% annually, respectively (P < 0.001). C‐statistics to discriminate outcomes at 1 and 5 years were 0.95 and 0.82 for TD and 0.80 and 0.76 for HBCs, respectively. Baseline hepatic fibrosis stage was worse with increasing risk score, with extensive fibrosis in 8% of the lowest versus 100% with the highest risk index (P < 0.001). The model was validated in 240 children from 11 additional centers and performed well. Conclusions The SCOPE index is a pediatric‐specific prognostic tool for PSC. It uses routinely obtained, objective data to predict a complicated clinical course. It correlates strongly with biopsy‐proven liver fibrosis. SCOPE can be used with families for shared decision making on clinical care based on a patient’s individual risk, and to account for variable disease progression when designing future clinical trials.

Oral Vancomycin or Ursodeoxycholic Acid for Pediatric Primary Sclerosing Cholangitis? The Uncontroversial Need for Randomized Controlled Trials

“…There was also no difference in histology nor in predictors of disease progression according to disease severity as defined by the Sclerosing Cholangitis Outcomes in Pediatrics (SCOPE) index. ( 7 ) As expected, patients with milder phenotypes (e.g., small‐duct PSC) more frequently achieved a biochemical response. In addition, patients treated initially with OVT had no increase in biochemical response compared to those treated with OVT following failure of UDCA (58% vs. 50%; P = 0.4).…”

“…The study by Deneau et al in this issue adds important information and, strikingly, highlights the need for randomized controlled trials (RCTs). ( 6 ) Drawing upon data from the groundbreaking Pediatric PSC Consortium, an international collaboration of >50 centers, which currently includes data from >1,000 patients, ( 3,6,7 ) Deneau et al performed a retrospective, propensity‐matched analysis of 264 children who received UDCA, OVT, or no treatment. They evaluated surrogate outcomes after 1 year and liver transplantation listing after 5 years.…”

Oral Vancomycin, Ursodeoxycholic Acid, or No Therapy for Pediatric Primary Sclerosing Cholangitis: A Matched Analysis

“…Whereas all management strategies showed reductions in GGT, none showed improvements in bilirubin, APRI, or biopsy‐proven fibrosis stage, which are more important markers of advanced disease and are more correlated with prognosis. ( 28 ) UDCA use in pediatric PSC is widespread, with many centers prescribing it for all or nearly all patients. The lack of transplant‐free survival benefit we observed is consistent with the results of numerous earlier clinical trials in adults.…”

“…( 29 ) This was true even though 3 times as many small duct PSC patients were included as in this analysis, a phenotype known to have favorable outcomes. ( 24,28 ) Two pilot randomized trials of OVT in adults suggested some potential benefits to biochemistry. In one study, biochemical improvement was greater in a group receiving a lower dose of 250 mg three times daily compared to the higher dose of 500 mg three times daily that is most commonly used in pediatric patients, and similar responses were observed in metronidazole‐treated patients.…”

“…We previously used data from 1,012 children with PSC to create a risk‐stratification and prognostic tool for pediatric PSC, the Sclerosing Cholangitis Outcomes in Pediatrics (SCOPE) index ( 28 ) shown in Table 1. SCOPE is based on total bilirubin, serum albumin, platelet count, GGT, and presence or absence of abnormal cholangiography and gives an integer index score from 0 to 11.…”