Pediatric Primary Sclerosing Cholangitis Research Articles

Caregiver-reported symptomburden and preferences for therapeutic goals in pediatric primary sclerosing cholangitis.

This study analyzed qualitative and quantitative survey responses from 51 pediatric primary sclerosing cholangitis (PSC) patients and caregivers using the PSC Partners Patient Registry-Our Voices survey. The most common symptoms reported by children/caregivers include: fatigue (71%), abdominal pain (69%), anxiety (59%), appetite loss (51%), insomnia (49%), and pruritus (45%). When experiencing symptoms at their worst, over half of patients/caregivers reported limitations in physically demanding activities (67%), work/school duties (63%), social life activities (55%), and activities for fun or exercise (53%). Over half of patients/caregivers expressed willingness to participate in clinical trials, however none reported ever participating in trials for new or investigational PSC drugs. This study revealed a substantial patient/caregiver-reported symptom burden for children with PSC that impacts quality of life and limits access to clinical trials. Future efforts should focus on developing patient-centered clinical endpoints for PSC trials, increasing trial availability for pediatric PSC patients, and reducing logistical barriers to trial involvement.

Single Center Experience of Oral Vancomycin Therapy in Young Patients with Primary Sclerosing Cholangitis: A Case Series

There is no single proven therapy that prolongs hepatic transplant-free survival in patients with primary sclerosing cholangitis (PSC). Oral vancomycin (OV) has shown some benefit in small pediatric and adult series. We describe the effect of OV on pediatric onset PSC at our tertiary hospital. This is a single-center, retrospective, descriptive case series involving patients (<21 years at diagnosis) with PSC on OV from 2001 till 2021. The therapy effect was assessed based on symptoms, biochemical labs, imaging and liver biopsy at six and twelve months, and then annually until therapy was discontinued. The inclusion criteria identified 17 patients. Baseline GGT (n = 17) was elevated among 88.2% which then normalized among 53.8% (n = 13) at six months and 55.6% (n = 9) at one year post-OV. Baseline ALT normalized in 58.8% (n = 17) at six months and 42.8% (n = 14) at one year. Imaging findings within one year of OV revealed improved/stable biliary findings among 66.7% (n = 8/12). No adverse events were reported. OV was associated with an improvement in bile duct injury marker (GGT) after at least six months of therapy, with no disease progression on imaging within one year of therapy.

Adult Primary Sclerosing Cholangitis (PSC) subjects have worse biliary disease at diagnosis compared to pediatric PSC subjects

IntroductionAdult Primary Sclerosing Cholangitis (PSC) subjects have worse outcomes compared to pediatric PSC subjects. The reasons for this observation are not completely understood. MethodsIn this single-center, retrospective (2005–17) study we compared clinical information, laboratory data, and previously published MRCP-based scores between 25 pediatric (0–18 years at diagnosis) and 45 adult (19 years and above) subjects with large duct PSC at the time of diagnosis. For each subject, radiologists determined MRCP-based parameters and scores after reviewing the MRCP images. ResultsThe median age at diagnosis for pediatric subjects was 14 years, while that of adult subjects was 39 years. At the time of diagnosis, adult subjects had a higher incidence of biliary complications like cholangitis and high-grade biliary stricture (27% vs. 6%, p = 0.003) and higher serum bilirubin (0.8 vs. 0.4 mg/dl, p = 0.01). MRCP analysis showed that adult subjects had a higher incidence of hilar lymph node enlargement (24.4% vs. 4%, p = 0.03) at diagnosis. Adult subjects had worse sum-IHD score (p = 0.003) and average-IHD score (p = 0.03). Age at diagnosis correlated with higher average-IHD (p = 0.002) and sum-IHD (p = 0.002) scores. Adult subjects had worse Anali score without contrast (p = 0.01) at diagnosis. MRCP-based extrahepatic duct parameters and scores were similar between groups. DiscussionAdult PSC subjects may have higher severity of disease at diagnosis compared to pediatric subjects. Future prospective cohort studies are required to confirm this hypothesis.

Natural history and prognosis of pediatric PSC with updates on management.

Natural history and prognosis of pediatric PSC with updates on management.

Long-term outcome after living donor liver transplantation compared to donation after brain death in autoimmune liver diseases: Experience from the European Liver Transplant Registry

Knowledge of living donor liver transplantation (LDLT) for autoimmune liver diseases (AILDs) is scarce. This study analyzed survival in LDLT recipients registered in the European Liver Transplant Registry with autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis (PSC) and the non-autoimmune disorder alcohol-related cirrhosis. In total, 29902 individuals enrolled between 1998 and 2017 were analyzed, including 1003 with LDLT. Survival from >90days after LDLT for AILDs in adults was 85.5%, 74.2%, and 58.0% after 5, 10, and 15years. Adjusted for recipient age, sex, and liver transplantation era, adult PSC patients receiving LDLT showed increased mortality compared to donation after brain death (DBD) (hazard ratio [HR]=1.95, 95% confidence interval [CI]=1.36-2.80, p<.001). Pediatric PSC patients showed also increased mortality >90days after LDLT compared to DBD (HR=3.00, 95% CI 1.04-8.70, p=.043). Multivariate analysis identified several risk factors for death in adult PSC patients receiving LDLT including a male donor (HR=2.49, p=.025). Adult PSC patients with LDLT versus DBD conferred increased mortality from disease recurrence (subdistribution hazard ratio [subHR]=5.36, p=.001) and biliary complications (subHR=4.40, p=.006) in multivariate analysis. While long-term outcome following LDLT for AILD is generally favorable, PSC patients with LDLT compared to DBD might be at increased risk of death.

Defining Primary Sclerosing Cholangitis: Results From an International Primary Sclerosing Cholangitis Study Group Consensus Process

Defining Primary Sclerosing Cholangitis: Results From an International Primary Sclerosing Cholangitis Study Group Consensus Process

Letter to the Editor: Oral Vancomycin Versus No Therapy for Pediatric Primary Sclerosing Cholangitis

In their recent study addressing efficacy oforal vancomycin (OVT) and ursodeoxycholic acid (UDCA) compared to no therapy in pediatric primary sclerosing cholangitis (PSC),Deneau et al.state: "OVT and UDCA are not effective treatments for PSC in children" [1]. Their study shows that the null hypothesis of no effect has not been rejected; a real effect might have been present but missed. Complications take up to 10 years to develop, but their median follow-up was just 4.2 years. The subsequent editorial [2] noted the limitations of a retrospective, propensity-matched study and argues cogently for the need to replace empiric practice with data from well-planned randomized controlled trials (RCTs).

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

Many children with primary sclerosing cholangitis (PSC) receive oral vancomycin therapy (OVT) or ursodeoxycholic acid (UDCA). There is a paucity of data on whether these medications improve outcomes. We analyzed retrospective data from the Pediatric PSC Consortium. Children treated with OVT were matched 1:1:1 to those treated with UDCA or managed with observation (no treatment) based on the closest propensity score, ensuring similar baseline characteristics. Two hundred sixty-four patients (88 each with OVT, UDCA, or observation) had matching propensity scores and were similar in demographics, phenotype, immunosuppression, baseline biochemistry, and hepatic fibrosis. After 1 year in an intention-to-treat analysis, all outcome metrics were similar regardless of treatment group. In OVT, UDCA, and untreated groups, respectively: Gamma-glutamyltransferase normalized in 53%, 49%, and 52% (P=not significant [NS]), liver fibrosis stage was improved in 20%, 13%, and 18% and worsened in 11%, 29%, and 18% (P=NS), and the 5-year probability of liver transplant listing was 21%, 10%, and 12% (P=NS). Favorable outcome was associated with having a mild phenotype of PSC and minimal hepatic fibrosis. We presented the largest-ever description of outcomes on OVT in PSC and compared them to carefully matched patients on UDCA or no therapy. Neither OVT nor UDCA showed improvement in outcomes compared to a strategy of observation. Patients progressed to end-stage liver disease at similar rates. Spontaneous normalization of biochemistry is common in children receiving no therapy, particularly in the majority of children with a mild phenotype and an early stage of disease. Placebo-controlled treatment trials are needed to identify effective treatments for pediatric PSC.

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

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. 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 5years 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. 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.

Vedolizumab Therapy in Children With Primary Sclerosing Cholangitis: Data From the Pediatric Primary Sclerosing Cholangitis Consortium.

Most patients with primary sclerosing cholangitis (PSC) also have inflammatory bowel disease (IBD). The liver and colon express MAdCAM-1, a target of lymphocyte homing integrins. Vedolizumab (VDZ) is an α4β7 integrin antibody used to treat IBD. We investigated liver outcomes in children with PSC-IBD treated with VDZ. Patients were identified within the Pediatric PSC Consortium, a multicenter research registry. Retrospective demographic, phenotypic, biochemical, radiological, histopathologic and IBD data for up to 1 year of VDZ therapy were collected. Liver biochemical and IBD responses were defined as: a 75% or greater reduction in initial γ-glutamyltransferase (GGT), or a GGT that fell to <50 IU/L and improved Mayo endoscopy grade or IBD activity scores after 9 to 12 months. Thirty-seven patients were identified from 19 centers. VDZ was initiated at median age of 16 years [IQR 15-18], 69% were male, 65% had large duct involvement, 19% had (Metavir F3/F4) fibrosis and 59% had ulcerative colitis. Of 32 patients with abnormal GGT at baseline, 22% had a liver biochemical response after 9 to 12 months. For IBD, 32% achieved remission, 30% had a clinical response, and 38% had no response. Final GGT after 9 to 12 months was 51 [IQR 28-71] in IBD patients in remission versus 127 [IQR 63-226] in those with active IBD, (P = 0.066). Liver biochemistry worsened over time in IBD unresponsive to VDZ but remained unchanged in IBD patients in remission. VDZ did not improve liver biochemistry in pediatric PSC-IBD. Progressive liver disease may be more common in patients with medically refractory IBD.

Magnetic Resonance Cholangiopancreatography Severity Predicts Disease Outcomes in Pediatric Primary Sclerosing Cholangitis: A Reliability and Validity Study.

Magnetic resonance cholangiopancreatography (MRCP) has not been assessed as a surrogate biomarker in pediatrics. We aimed to determine the inter‐rater reliability, prognostic utility, and construct validity of the modified Majoie endoscopic retrograde cholangiopancreatography classification applied to MRCP in a pediatric primary sclerosing cholangitis (PSC) cohort. This single‐center, retrospective, cohort study included children with PSC undergoing diagnostic MRCP between 2008 and 2016. Six variations of the Majoie classification were examined: 1) intrahepatic duct (IHD) score, 2) extrahepatic duct (EHD) score (representing the worst intrahepatic and extrahepatic regions, respectively), 3) sum IHD‐EHD score, 4) average IHD score, 5) average EHD score, and 6) sum average IHD‐EHD score. Inter‐rater reliability was assessed using weighted kappas and intraclass correlation coefficients (ICCs). Ability to predict time to PSC‐related complications (ascites, esophageal varices, variceal bleed, liver transplant [LT], or cholangiocarcinoma) (primary outcome) and LT (secondary outcome) was assessed with Harrell’s concordance statistic (c‐statistic) and univariate/multivariable survival analysis. Construct validity was further assessed with Spearman correlations. Forty‐five children were included (67% boys; median, 13.6 years). The inter‐rater reliability of MRCP scores was substantial to excellent (kappas/ICCs, 0.78‐0.82). The sum IHD‐EHD score had the best predictive ability for time to PSC complication and LT (c‐statistic, 0.80 and SE, 0.06; and c‐statistic, 0.97 and SE, 0.01, respectively). Higher MRCP scores were independently associated with a higher rate of PSC‐related complications, even after adjusting for the PSC Mayo risk score (hazard ratio, 1.74; 95% confidence interval, 1.14‐2.). MRCP sum scores correlated significantly with METAVIR fibrosis stage, total bilirubin, and platelets (r = 0.42, r = 0.33, r = −0.31, respectively; P < 0.05). Conclusion: An MRCP score incorporating the worst affected intrahepatic and extrahepatic regions is reliable and predicts meaningful outcomes in pediatric PSC. Next steps include prospective validation and responsiveness assessment.

Long-term outcomes of pediatric-onset primary sclerosing cholangitis: A single-center experience in Japan.

Primary sclerosing cholangitis (PSC) is very rare in Japan. Although a large-scale cohort study of 781 pediatric-onset PSC patients in Europe and North America showed that the 5-year survival with native liver was 88%, the long-term outcomes of pediatric-onset PSC in Japan are unknown. Here, we evaluated the clinical outcomes of pediatric-onset PSC in Japan. We carried out a retrospective cohort study with a medical records review of pediatric PSC patients diagnosed between 1986 and 2017 at a single center. The PSC diagnoses were based on cholangiography, liver histology, and biochemical findings. The patients' survival was analyzed using the Kaplan-Meier method. Prognostic factors were determined by univariate and multivariate analyses using the Cox proportional hazards regression model. We identified 39 pediatric-onset PSC patients (22 boys, 17 girls). The median age at diagnosis was 9years (interquartile range 6.0-13.5years). The median follow-up period was 5.5years (interquartile range 3.4-8.7years). The phenotypes of PSC-autoimmune hepatitis, PSC-inflammatory bowel disease, and small-duct PSC were diagnosed in 13 (33.3%), 36 out of 38 (94.8%), and three (7.7%) patients, respectively. The 5-year liver transplantation-free survival of the whole cohort was 93.5%. Nine patients underwent liver transplantation, and four of these nine cases resulted in death. Both the univariate and multivariate analyses showed that the phenotype of "PSC-autoimmune hepatitis overlap" was an independent poor prognostic factor. The overall survival of pediatric-onset PSC in Japan was comparable to those in Western countries. The phenotype of PSC-autoimmune hepatitis was identified as a prognostic factor associated with a poorer long-term outcome.

A Prospective Trial of Withdrawal and Reinstitution of Ursodeoxycholic Acid in Pediatric Primary Sclerosing Cholangitis.

Ursodeoxycholic acid (UDCA) is commonly used to treat several liver disorders in adults and children, including primary sclerosing cholangitis (PSC) for which it is not U.S. Food and Drug Administration approved. UDCA treatment has an uncertain impact on disease outcomes and has been reported in high doses to be associated with worse outcome in adults with PSC. In this context, controlled withdrawal and reintroduction of UDCA in children with PSC were studied. Prior to study initiation, participants were required to have alanine aminotransferase (ALT) and gamma‐glutamyl transpeptidase (GGT) <2 times the upper limit of normal on stable UDCA dosing. The study included four phases: I (stable dosing), II (50% UDCA reduction), III (UDCA discontinuation), IV (UDCA reintroduction), with a primary endpoint of change in ALT and GGT between phases I and III. We enrolled 27 participants (22 completed) between March 2011 and June 2016. Changes in mean ALT and GGT between phases I and III were ALT, +29.5 IU/L (P = 0.105) and GGT, +60.4 IU/L (P = 0.003). In 7 participants, ALT and GGT ≤29 IU/L did not rise above 29 IU/L (null response group). Eight participants had increases of ALT or GGT >100 IU/L (flare group). None developed elevated bilirubin. All flares responded to UDCA reinstitution. Serum GGT, interleukin‐8, and tumor necrosis factor α levels were higher in the flare group at baseline. Liver biochemistries increased in children with PSC during controlled UDCA withdrawal; one third increased above 100 IU/L and one third remained normal during UDCA withdrawal. Conclusion: The impact of prolonged UDCA use in childhood PSC and the significance of a biochemical flare are unclear. Further studies of the natural history and treatment of pediatric PSC and UDCA use are needed.

Cholangiocarcinoma in Patients with Primary Sclerosing Cholangitis (PSC): a Comprehensive Review.

Cholangiocarcinoma (CCA) is the most common malignancy in patients with primary sclerosing cholangitis (PSC) and carries a high rate of mortality. Although the pathogenesis of CCA in PSC is largely unknown, inflammation-driven carcinogenesis concomitant with various genetic and epigenetic abnormalities are underlying factors. The majority of CCA cases develop from a dominant stricture (DS), which is defined as a stricture with a diameter < 1.5mm in the common bile duct or < 1.0mm in the hepatic duct. In PSC patients presenting with an abrupt aggravation of jaundice, pain, fatigue, pruritus, weight loss, or worsening liver biochemistries, CCA should be suspected and evaluated utilizing a variety of diagnostic modalities. However, early recognition of CCA in PSC remains a major challenge. Importantly, 30-50% of CCA in PSC patients are observed within the first year following the diagnosis of PSC followed by an annual incidence ranging from 0.5 to 1.5 per 100 persons, which is nearly 10 to 1000 times higher than that in the general population. Cumulative 5-year, 10-year, and lifetime incidences are 7%, 8-11%, and 9-20%, respectively. When PSC-associated CCA is diagnosed, most tumors are unresectable, and no effective medications are available. Given the poor therapeutic outcome, the surveillance and management of PSC patients who are at an increased risk of developing CCA are of importance. Such patients include older males with large-duct PSC and possibly concurrent ulcerative colitis. Thus, more attention should be paid to patients with these clinical features, in particular within the first year after PSC diagnosis. In contrast, CCA is less frequently observed in pediatric or female PSC patients or in those with small-duct PSC or concurrent Crohn's disease. Recently, new biomarkers such as antibodies to glycoprotein 2 have been found to be associated with an increased risk of developing CCA in PSC. Herein, we review the literature on the pathogenesis, incidence, clinical features, and risk factors, with a focus on various diagnostic modalities of PSC-associated CCA.

Gamma Glutamyltransferase Reduction Is Associated With Favorable Outcomes in Pediatric Primary Sclerosing Cholangitis.

Adverse clinical events in primary sclerosing cholangitis (PSC) happen too slowly to capture during clinical trials. Surrogate endpoints are needed, but no such validated endpoints exist for children with PSC. We evaluated the association between gamma glutamyltransferase (GGT) reduction and long‐term outcomes in pediatric PSC patients. We evaluated GGT normalization (< 50 IU/L) at 1 year among a multicenter cohort of children with PSC who did or did not receive treatment with ursodeoxycholic acid (UDCA). We compared rates of event‐free survival (no portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or liver‐related death) at 5 years. Of the 287 children, mean age of 11.4 years old, UDCA was used in 81% at a mean dose of 17 mg/kg/day. Treated and untreated groups had similar GGT at diagnosis (314 versus 300, P= not significant [NS]). The mean GGT was reduced at 1 year in both groups, with lower values seen in treated (versus untreated) patients (99 versus 175, P= 0.002), but 5‐year event‐free survival was similar (74% versus 77%, P= NS). In patients with GGT normalization (versus no normalization) by 1 year, regardless of UDCA treatment status, 5‐year event‐free survival was better (91% versus 67%, P< 0.001). Similarly, larger reduction in GGT over 1 year (> 75% versus < 25% reduction) was also associated with improved outcome (5‐year event‐free survival 88% versus 61%, P= 0.005). Conclusion:A GGT < 50 and/or GGT reduction of > 75% by 1 year after PSC diagnosis predicts favorable 5‐year outcomes in children. GGT has promise as a potential surrogate endpoint in future clinical trials for pediatric PSC.

Post-Transplant Disease Recurrence in Pediatric PSC.

Review the current knowledge about recurrent primary sclerosing cholangitis (rPSC) after transplant in children. Recurrent PSC is a significant complication that afflicts 16% of children after liver transplantation for primary sclerosing cholangitis (PSC) at a median onset of 38months post-transplant. Possible risk factors include younger age at PSC diagnosis or transplant, the presence of overlap syndrome or IBD, and post-transplant induction with thymoglobulin. rPSC impairs the patient's quality of life and can be detrimental to the graft. Preventive options and therapeutic measures are limited. Ursodeoxycholic acid is widely used, but its effect on long-term outcome is unknown. Vancomycin can improve the biochemical profile of rPSC, but it remains unknown whether it halts the disease progression. Pediatric liver transplant for primary sclerosis cholangitis can be complicated by recurrence of the disease, which portends poor outcomes. Although few risk factors have been implicated, larger studies with longer follow-ups are needed to characterize cardinal risk factors for rPSC, as well as evaluate possible preventative and therapeutic options.

Mo1446 - Initial Results of the Wuppsc Study – Prospective Multicenter Withdrawal of Ursodeoxycholic Acid in Pediatric Primary Sclerosing Cholangitis (PSC)

Mo1446 - Initial Results of the Wuppsc Study – Prospective Multicenter Withdrawal of Ursodeoxycholic Acid in Pediatric Primary Sclerosing Cholangitis (PSC)

Lack of Correlation of Liver Tests With Fibrosis Stage at Diagnosis in Pediatric Primary Sclerosing Cholangitis.

The aims of this study were to characterize pediatric primary sclerosing cholangitis (PSC) at a regional referral-based institution, including scoring of biliary stricturing and liver fibrosis and correlation analyses of scores with serum liver tests, to identify biomarkers of disease severity. A retrospective review of 39 PSC subjects was performed, with collection of demographic and outcomes data. Magnetic resonance cholangiopancreaticogram (MRCP) and liver biopsies were re-reviewed and scores of stricturing and fibrosis were correlated with serum liver tests. Average age at PSC diagnosis was 11.2 years, 74% had inflammatory bowel disease and 51% had autoimmune hepatitis. Despite 83% with symptoms at presentation, only ∼1/3 were symptomatic at a mean follow-up of 4.1 years. Using a validated MRCP biliary scoring system, the mean intrahepatic score was 1.1 (out of 4) and extrahepatic score was 1.0 (out of 3). The mean Ishak liver fibrosis stage was 3.5 (out of 6) and 33% had cirrhosis. 92% were alive with their native liver and 5% had a liver transplant. Serum biomarker analyses revealed no correlation between Ishak liver fibrosis stage or MRCP score and laboratory values. Pediatric PSC patients cared for at a regional referral center had relatively mild disease compared with previously published reports, with low MRCP stricture scores despite significant liver fibrosis. Liver tests at presentation did not correlate with MRCP stricture score or liver fibrosis stage, suggesting the need for future studies to identify potential biomarkers of disease severity.

Usefulness of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein in children with primary sclerosing cholangitis.

Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+ -M2BP) is a novel serum marker of hepatic fibrosis in adults with chronic hepatitis C. However, it remains unclear whether serum WFA+ -M2BP levels are associated with the progression of liver histology in primary sclerosing cholangitis (PSC). Twenty-eight children and adolescents with pediatric-onset PSC (male:female patient ratio,20:8; median age at diagnosis, 9years) were enrolled in this study. The relation between serum WFA+ -M2BP levels and clinical characteristics was retrospectively evaluated. Moreover, receiver operating characteristic (ROC) analysis was used to determine whether serum WFA+ -M2BP levels could be a reliable marker to identify PSC patients with advanced liver histology. According to the Ludwig classification of liver histological stage, 28 patients were classified into the four stages. The WFA+ -M2BP level, aspartate aminotransferase (AST) to platelet ratio index (APRI), and hyaluronic acid correlated significantly with liver histological stage. Moreover, WFA+ -M2BP showed a significant positive correlation (P < 0.05) with autoimmune hepatitis overlap, AST, alanine aminotransferase (ALT), γ-glutamyltransferase, total bilirubin, immunoglobulin G, APRI, and hyaluronic acid. A ROC analysis was undertaken to distinguish the patients with advanced stage disease (stage 3-4) from those with early stage disease (stage 0-2). It showed that WFA+ -M2BP yielded the highest area under the ROC curve value (0.898) among four surrogate makers (APRI, 0.850; Fibrosis-4 index, 0.806; and AST/ALT ratio, 0.802). Moreover, WFA+ -M2BP yielded the highest sensitivity, specificity, positive predictive value, and negative predictive value among the four markers. Serum WFA+ -M2BP levels are useful to identify patients with advanced liver histology in pediatric PSC.

Unique Inflammatory Bowel Disease Phenotype of Pediatric Primary Sclerosing Cholangitis

In adults, primary sclerosing cholangitis (PSC), a cholestatic liver disease characterized by inflammation/fibrosis of intra/extrahepatic bile ducts, associates with a milder form of inflammatory bowel disease (IBD), particularly ulcerative colitis (UC). The pediatric PSC-IBD phenotype is less well characterized. We performed a retrospective, single-center study examining patients with PSC-IBD at Texas Children's Hospital between 2000 and 2015. IBD-phenotype (Modified Montreal Classification), medications, laboratory values, endoscopic records, and IBD-based hospital admissions were collected. PSC-UC phenotype was compared to UC, non-PSC patients (n = 95) from Texas Children's Hospital. Elevated gamma-glutamyl transpeptidase levels were compared to calprotectin levels and IBD-flare activity, that is, gastrointestinal symptoms resulting in office/emergency department visits or hospital admission. Of 39 patients with PSC-IBD, 34 (87.2%) had UC (PSC-UC) and 5 (12.8%) had Crohn disease. Pancolitis was more common in PSC-UC than UC, non-PSC (96.3%, 64%, P = 0.0009). Patients with PSC-UC required less treatment with steroids (76.5%, 91.6%, P = 0.0326) or infliximab (8.8%, 37.9%, P = 0.0011), and fewer had at least 1 IBD-related hospital admission (32.4%, 63.2%, P = 0.0025) than UC, non-PSC. Progression to colectomy was significantly less (5.8%, 24.2%, P = 0.0223) in PSC-UC. Median diagnosis-to-colectomy time tended to be longer in PSC-UC (6.37, 2.5 years, P = 0.0792). In 2 smaller subsets, gamma-glutamyl transpeptidase did not correlate with calprotectin in PSC-UC (n = 11, P = 0.7922) and less strongly associated with IBD-flares in PSC-UC than UC, non-PSC (n = 33, n = 67; 15.2%, 41.8%, P = 0.0120). Pediatric PSC appears to associate with milder pancolitic-UC. PSC and IBD activity do not appear to correlate. Our findings may provide useful information toward etiology and management of pediatric PSC-IBD.