Browsing by Author "Furuya, Katryn N."

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    Colorectal Dysplasia and Cancer in Pediatric-Onset Ulcerative Colitis Associated With Primary Sclerosing Cholangitis
    (Elsevier, 2021) El-Matary, Wael; Guthery, Stephen L.; Amir, Achiya Z.; DiGuglielmo, Matthew; Draijer, Laura G.; Furuya, Katryn N.; Gupta, Nitika; Hochberg, Jessica T.; Horslen, Simon; Kerkar, Nanda; Koot, Bart G. P.; Laborda, Trevor J.; Loomes, Kathleen M.; Mack, Cara; Martinez, Mercedes; Miethke, Alexander; Miloh, Tamir; Mogul, Douglas; Mohammed, Saeed; Moroz, Stacy; Ovchinsky, Nadia; Perito, Emily R.; Rao, Girish; Ricciuto, Amanda; Sathya, Pushpa; Schwarz, Kathleen B.; Shah, Uzma; Singh, Ruchi; Soufi, Nisreen; Valentino, Pamela L.; Zizzo, Andréanne; Deneau, Mark R.; Pediatrics, School of Medicine
    Inflammatory bowel disease (IBD), especially when associated with primary sclerosing cholangitis (PSC), is a risk factor for developing colorectal cancer (CRC). We aimed to determine the incidence of CRC in a large cohort of pediatric-onset PSC-ulcerative colitis (UC) patients.
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    Oral Vancomycin, Ursodeoxycholic Acid, or No Therapy for Pediatric Primary Sclerosing Cholangitis: A Matched Analysis
    (Wolters Kluwer, 2021) Deneau, Mark R.; Mack, Cara; Mogul, Douglas; Perito, Emily R.; Valentino, Pamela L.; Amir, Achiya Z.; DiGuglielmo, Matthew; Draijer, Laura G.; El-Matary, Wael; Furuya, Katryn N.; Gupta, Nitika; Hochberg, Jessica T.; Horslen, Simon; Jensen, M. Kyle; Jonas, Maureen M.; Kerkar, Nanda; Koot, Bart G. P.; Laborda, Trevor J.; Lee, Christine K.; Loomes, Kathleen M.; Martinez, Mercedes; Miethke, Alexander; Miloh, Tamir; Mohammad, Saeed; Ovchinsky, Nadia; Rao, Girish; Ricciuto, Amanda; Sathya, Pushpa; Schwarz, Kathleen B.; Shah, Uzma; Singh, Ruchi; Vitola, Bernadette; Zizzo, Andréanne; Guthery, Stephen L.; Pediatrics, School of Medicine
    Background and aims: 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. Approach and results: 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. Conclusions: 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.
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    Recurrence of Primary Sclerosing Cholangitis After Liver Transplant in Children: An International Observational Study
    (Wolters Kluwer, 2021) Martinez, Mercedes; Perito, Emily R.; Valentino, Pamela; Mack, Cara L.; Aumar, Madeleine; Broderick, Annemarie; Draijer, Laura G.; Fagundes, Eleonora D. T.; Furuya, Katryn N.; Gupta, Nitika; Horslen, Simon; Jonas, Maureen M.; Kamath, Binita M.; Kerkar, Nanda; Kim, Kyung Mo; Kolho, Kaija-Leena; Koot, Bart G. P.; Laborda, Trevor J.; Lee, Christine K.; Loomes, Kathleen M.; Miloh, Tamir; Mogul, Douglas; Mohammed, Saeed; Ovchinsky, Nadia; Rao, Girish; Ricciuto, Amanda; Rodrigues Ferreira, Alexandre; Schwarz, Kathleen B.; Smolka, Vratislav; Tanaka, Atsushi; Tessier, Mary E. M.; Venkat, Venna L.; Vitola, Bernadette E.; Woynarowski, Marek; Zerofsky, Melissa; Deneau, Mark R.; Pediatrics, School of Medicine
    Background and aims: Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children. Approach and results: We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow-up. The primary outcome, rPSC, was defined using Graziadei criteria. Median follow-up after LT was 3 years (interquartile range 1.1-6.1). rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively. Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01). Inflammatory bowel disease was more prevalent in the rPSC group (86% vs. 66%; P = 0.025). After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04). In those with rPSC, 43% developed complications of portal hypertension, were relisted for LT, or died within 2 years of the diagnosis. Mortality was higher in the rPSC group (11.1% vs. 2.9%; P = 0.05). Conclusions: The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune-reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC, to lay the foundation for developing new therapies and improve outcomes in this challenging population.
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    The Frequency and Potential Implications of HFE Genetic Variants in Children With Cystic Fibrosis
    (Wiley, 2025) Huang, Leslie; Lai, HuiChuan J.; Furuya, Katryn N.; Antos, Nicholas J.; Asfour, Fadi; Boyne, Kathleen L.; Howenstine, Michelle; Rock, Michael J.; Sawicki, Gregory S.; Gaffin, Jonathan M.; Worthey, Elizabeth A.; Farrell, Philip M.; Pediatrics, School of Medicine
    Background: Genetic modifiers have been identified that increase the risks of lung disease and other complications, such as diabetes in people with cystic fibrosis (CF). Variants in the hemochromatosis gene (HFE) were reported in a study of adults to be associated with worse lung disease. Objectives: To ascertain the frequency of HFE variants, particularly C282Y (c.845G > A) and H63D (c.187C > G) and to determine if they are associated with variations in the onset and early severity of CF lung disease as well as abnormalities in iron status. Design: We studied with whole genome sequencing and clinical outcome measures in a cohort of 104 children with CF at 5-6 years old who were previously found to show an association between aggregated genetic modifiers and an earlier onset and a more severe lung disease phenotype. Results: In our cohort, 23% have H63D and 11% have C282Y. Lung function at age 6 years and Pseudomonas aeruginosa infections did not differ by HFE variants, but having C282Y was associated with more pulmonary exacerbations in the first 6 years of life. Three patients have H63D/C282Y genotype, and all showed phenotypic expression of hemochromatosis with abnormal iron indices. Conclusion: Our study revealed that the presence of HFE variant C282Y in people with CF may lead to more severe lung disease manifestations beginning in early childhood. There is a risk of hemochromatosis in CF patients with two HFE variants, and thus they should be followed for evidence of iron overload.
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    The Sclerosing Cholangitis Outcomes in Pediatrics (SCOPE) Index: A Prognostic Tool for Children
    (Wolters Kluwer, 2021) Deneau, Mark R.; Mack, Cara; Perito, Emily R.; Ricciuto, Amanda; Valentino, Pamela L.; Amin, Mansi; Amir, Achiya Z.; Aumar, Madeleine; Auth, Marcus; Broderick, Annemarie; DiGuglielmo, Matthew; Draijer, Laura G.; Druve Tavares Fagundes, Eleonora; El-Matary, Wael; Ferrari, Federica; Furuya, Katryn N.; Gupta, Nitika; Hochberg, Jessica T.; Homan, Matjaz; Horslen, Simon; Iorio, Raffaele; Jensen, M. Kyle; Jonas, Maureen M.; Kamath, Binita M.; Kerkar, Nanda; Kim, Kyung Mo; Kolho, Kaija-Leena; Koot, Bart G. P.; Laborda, Trevor J.; Lee, Christine K.; Loomes, Kathleen M.; Martinez, Mercedes; Miethke, Alexander; Miloh, Tamir; Mogul, Douglas; Mohammad, Saeed; Mohan, Parvathi; Moroz, Stacy; Ovchinsky, Nadia; Palle, Sirish; Papadopoulou, Alexandra; Rao, Girish; Rodrigues Ferreira, Alexandre; Sathya, Pushpa; Schwarz, Kathleen B.; Shah, Uzma; Shteyer, Eyal; Singh, Ruchi; Smolka, Vratislav; Soufi, Nisreen; Tanaka, Atsushi; Varier, Raghu; Vitola, Bernadette; Woynarowski, Marek; Zerofsky, Melissa; Zizzo, Andréanne; Guthery, Stephen L.; Pediatrics, School of Medicine
    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.