About

Kathleen M. Loomes, MD, is a Professor of Pediatrics specializing in Gastroenterology, Hepatology, and Nutrition at the Children's Hospital of Philadelphia. She holds multiple roles including Attending Physician at The Children's Hospital of Philadelphia, Consultant in Pediatric Gastroenterology at the Hospital of the University of Pennsylvania, and Pennsylvania Hospital in Philadelphia. Dr. Loomes is the Director of the Fred and Suzanne Biesecker Pediatric Liver Center at The Children's Hospital of Philadelphia and serves as the Section Chief of Research in the Division of Pediatric Gastroenterology, Hepatology, and Nutrition. Her educational background includes a B.A. in Biology from Rice University, where she graduated Cum laude in 1988, and an M.D. from the University of Texas Southwestern Medical School in 1992. Her research contributions include studies on pediatric liver diseases, immune responses in liver failure, biliary atresia, and growth charts for children with Alagille syndrome, among others.

Research topics

• Internal medicine
• Medicine
• Gastroenterology
• Pediatrics
• Surgery
• Genetics

Selected publications

• From supportive to targeted treatment strategies: the changing landscape of therapeutics in Alagille syndrome

  Expert Opinion on Therapeutic Targets · 2026-05-18

  articleSenior authorCorresponding
  PublisherDOI

• Demographic Factors and Biliary Atresia: A Childhood Liver Disease Research Network Study

  PEDIATRICS · 2026-02-19

  article

  OBJECTIVE: To test the hypothesis that community deprivation, race, and ethnicity lead to decreased likelihood of undergoing hepatoportoenterostomy, older age at surgery, decreased likelihood of achieving successful bile drainage, and lower rates of native liver survival for infants with biliary atresia. METHODS: We analyzed a prospectively enrolled cohort of infants with biliary atresia from the Childhood Liver Disease Research Network (ChiLDReN) that reflects the demographics of the US population. We tested the association between demographic, clinical, and anatomic variables and the probability of undergoing hepatoportoenterostomy, age at surgery, success of surgical intervention, and native liver survival using linear and logistic regression. RESULTS: Seven hundred nineteen infants with biliary atresia from 15 centers met study inclusion criteria and 672 (93.5%) underwent hepatoportoenterostomy. After adjusting for potential confounders, Asian race (odds ratio [OR] = 0.21, 0.06-0.77), Hispanic ethnicity (OR = 0.33, 0.14-0.76), and community deprivation (0.71 per 0.1 increase, 0.52-0.97) were independently associated with decreased probability of undergoing hepatoportoenterostomy. Each 10% increase in community deprivation increased the age at hepatoportoenterostomy by approximately two-and-one-third days (estimate 2.31; P = .48). Black/African American infants were approximately 9 days older than white infants at the time of operation (estimate 9.19; P = .01), while age at hepatoportoenterostomy (OR = 0.90, P = .01) and successful bile drainage at 3 months (OR = 26.15, P < .01) were independently associated with native liver survival. CONCLUSIONS: Community deprivation, race, and ethnicity are associated with both lower hepatoportoenterostomy rates and older age at the time of operation, whereas clinical and anatomic variables are associated with successful biliary drainage and native liver survival.

  PublisherDOI

• CD8 TRM-like T cells expressing perforin and IFN-γ define a pediatric activated T-cell acute liver failure endotype

  Hepatology Communications · 2026-03-31

  articleOpen access

  BACKGROUND: Activated T-cell pediatric acute liver failure (TC-PALF) is the most common cause of non-acetaminophen PALF, with poor transplant-free survival. Livers in TC-PALF are infiltrated by effector cytotoxic T lymphocytes with markers of tissue-resident memory function (CD8 Trm) and an interferon gamma (IFNγ) transcriptional signature. The PALF-Immune Response Network (PALF-IRN) and the prospective TReatment for ImmUne-Mediated PathopHysiology (TRIUMPH) clinical trial (NCT04862221) aim to characterize the TC-PALF immune pathology and utility of T-cell directed therapy to improve transplant-free survival. METHODS: TRIUMPH patients with TC-PALF were compared with healthy children and disease controls utilizing multiparameter flow cytometry and 3' single-cell RNA sequencing from peripheral blood mononuclear cells. TC-PALF patient serum was compared with healthy children and those with PALF from other causes, utilizing the Olink Inflammation I 384 protein assay. RESULTS: Two distinct endotypes of TC-PALF were identified, which differed in flow cytometry CD8+ Perforin1 (Prf) expression and liver biopsy staining of Prf. TC-PALF patients with high CD8+ Prf (TC-PALF High Prf) had monocytosis, with a unique circulating CD8 IFNγ+ Trm-like population and IFNγ-responsive CD14/CD16 monocyte ligand-receptor interaction. TC-PALF patients with normal CD8+ Prf expression had hypergammaglobulinemia, an increase in class-switched B-cells, and a decrease in serum inflammatory proteins associated with myeloid activation. CONCLUSIONS: TC-PALF high Prf patients have a unique circulating CD8+ IFNγ+ Trm-like population accompanied by monocyte proliferation and activation. Further understanding of the role of IFNγ in TC-PALF High Prf may provide a therapeutic target for this endotype to improve transplant-free survival.

  PublisherDOI

• Prospective Multicenter Longitudinal Measurement of Liver Stiffness in School-Age Children With Cholestatic Liver Disease

  Gastro Hep Advances · 2025-01-01

  articleOpen access

  Background and Aims: A multicenter prospective longitudinal study of vibration-controlled transient elastography (VCTE) in school-age children with biliary atresia (BA), alpha-1 antitrypsin deficiency (a1-AT) and Alagille syndrome (ALGS) was undertaken to test the hypothesis that there would be measurable disease progression over 2 years. Methods: Vibration-controlled transient elastography was performed annually for 2 years in children with BA, a1-AT and ALGS. Results: Valid liver stiffness measurement (LSM) was determined at baseline/second follow-up in 254/180 (71%), 104/58 (56%) and 100/61 (61%) participants (mean elapsed time 2.27 years) with BA, a1-AT and ALGS, respectively. Modeling did not reveal a relationship between LSM and time since baseline: BA 1.2% (-1.6, 4.2%), a1-AT 0.1% (-3.8, 4.2%), and ALGS 3.6% (-2.9, 10.5%) LSM (% change/year; mean [95% confidence interval]). Similarly, mean LSM did not change significantly from baseline to visit 2 (BA 13.6 + 11.0 vs 15.1 + 12.8; a1-AT 7.8 + 5.1 vs 8.5 + 7.6; ALGS 10.6 + 9.4 vs 12.2 + 12.1 kPa, mean + standard deviation). Albumin and total bilirubin levels did not change in these participants. Platelet counts dropped at rates that were similar to a national representative sample, the National Health and Nutrition Examination Survey (ie, 5000 to 7000/μL per year). Conclusion: Surprisingly, longitudinal measurement of LSM and laboratory parameters of liver disease severity over 2 years in school-age children with compensated BA, a1-AT, and ALGS did not reveal significant change, consistent with slow progression of cholestatic liver disease in this age group. These findings have implications for both clinical care and interventional trials in this patient population.

  PublisherDOI

• Acute Liver Failure Unmasking XIAP Deficiency in Very Early-Onset Inflammatory Bowel Disease

  Journal of Human Immunity · 2025-04-25

  articleOpen access

  Introduction X-linked inhibitor of apoptosis (XIAP) deficiency is a rare inborn error of immunity with particularly pleiomorphic spectrum of manifestations. These include hemophagocytic lymphohistiocytosis (HLH) with and without primary EBV infection, inflammatory bowel disease (IBD), uveitis, and episodic fevers. Liver manifestations have been rarely reported. Herein we describe severe acute liver failure (ALF) in a patient with very early-onset IBD found to have XIAP deficiency. Case Presentation The patient presented at 5 years of age with intermittent bloody stools, a perianal skin tag, and a history of intermittent fevers since infancy. Endoscopic evaluation at 6 years of age showed ulcerations and histologic colitis and granulomas. He was initiated on infliximab with good clinical response. Concurrent with his IBD evaluation, he was noted to have elevated liver enzymes. Twenty-one months after diagnosis, he developed fever, right upper quadrant pain, nausea, scleral icterus, liver enzymes to the 2000s, and cholestasis without synthetic dysfunction. EBV serologies were IgM positive. Transaminases improved spontaneously, but five days later, he re-presented with marked transaminitis, worsened cholestasis, and new synthetic dysfunction. He was transferred to a tertiary academic referral center ICU with high fevers and encephalopathy for management of ALF. HLH biomarkers were only modestly elevated: ferritin 290, Hgb 9.2, Plts 177, ANC 1620, fibrinogen 103, sIL-2Ra 1500, IFNg 128, and CXCL9 2959. EBV serologies and serial PCRs were negative. IL-18 was 12079. He was treated with IV glucocorticoids and emapalumab with stabilization. Flow cytometry showed XIAP deficiency, and anakinra was added with gradual resolution of liver dysfunction. Whole-genome sequencing revealed an XIAP frameshift variant (c.1021_1022del, p.(N341Yfs*8)). Emapalumab was replaced with ruxolitinib as the patient was preparing for hematopoietic stem cell transplant. Discussion XIAP-deficiency is remarkable for its range and severity of inflammatory phenotypes, including HLH and refractory IBD. Here we present a rare case of ALF in XIAP-deficiency. Antecedent, transient EBV infection was a likely trigger. His ALF improved with steroids, emapalumab, and IL-1 blockade. A high index of suspicion for immune dysregulation should be employed in all cases of VEO-IBD and/or liver failure. Figure 1. Laboratory trends and therapeutics. Day 0 represents initial hospitalization for acute liver failure.

  PublisherDOI

• Phenotypic Divergence of <i>JAG1</i> ‐ and <i>NOTCH2</i> ‐Associated Alagille Syndrome &amp; Disease‐Specific <i>NOTCH2</i> Variant Classification Guidelines

  Liver International · 2025-07-31 · 3 citations

  articleOpen access

  BACKGROUND & AIMS: Alagille syndrome (ALGS) is a rare, autosomal dominant disorder with high phenotypic heterogeneity. Disease-causing variants are primarily identified in Jagged1 (JAG1), with fewer reported in NOTCH2. JAG1 variants cause disease through a mechanism of haploinsufficiency, but the mechanism for NOTCH2 variants is not completely understood, making classification of variants more challenging. Using a large, international patient cohort acquired through the Global ALagille Alliance (GALA) study, we sought to improve classification of NOTCH2 variants and study phenotypic differences between NOTCH2- and JAG1-related disease. METHODS: Clinical and molecular data from 952 individuals with ALGS in GALA were analysed and disease features compared between those with JAG1 (n = 902) and NOTCH2 (n = 34) variants. Previously reported and newly identified NOTCH2 variants were reinterpreted based on disease-specific modifications to the American College of Medical Genetics and Genomics (ACMG) guidelines. The Kaplan-Meier method was utilised to assess native liver survival (NLS) and overall survival (OS) and gene comparisons were made with the log-rank test. RESULTS: Thirty NOTCH2 variants, including 18 novel variants, were identified and classified in our GALA cohort. Phenotypic analyses revealed a significantly lower incidence of characteristic facies, posterior embryotoxon, cardiac involvement and butterfly vertebrae in individuals with NOTCH2 variants compared to those with JAG1 variants (p < 0.001). No differences were identified in NLS or OS. Review of 61 previously reported NOTCH2 variants resulted in the re-classification of 19 likely pathogenic or pathogenic to VOUS (31.1%) with less than half retaining their originally published classification (34.4%; n = 21). CONCLUSIONS: We report on a large global study on NOTCH2 genetics and phenotype, which increases the number of reported NOTCH2 variants by 30%. All variants were reclassified using current guidelines, and comparison of the JAG1 and NOTCH2 cohorts demonstrates clear phenotypic divergence between these groups. These data suggest that reliance on classical clinical phenotyping may miss patients with NOTCH2-related disease and supports an inclusive approach to genetic testing.

  PublisherOA PDFDOI

• SPNing our wheels—Pancreatic solid pseudopapillary neoplasm as an extraluminal etiology of persistent duodenal ulceration

  JPGN Reports · 2025-02-25

  articleOpen access

  Pediatric upper gastrointestinal (GI) bleeding secondary to duodenal ulceration is a potentially serious and life-threatening condition with a broad differential diagnosis. We present a pediatric case of a pancreatic head solid pseudopapillary neoplasm (SPN) presenting with duodenal ulceration and recurrent upper GI bleeding. This case highlights pancreatic SPNs as a rare extrinsic cause of duodenal ulceration. Recurrence and progression in size and extent of a duodenal ulceration in the absence of other inciting factors should raise suspicion for an extraluminal etiology.

  PublisherOA PDFDOI

• Real-world outcomes of delandistrogene moxeparvovec gene therapy: Motor outcomes and emerging safety concerns

  Molecular Therapy · 2025-10-05 · 3 citations

  articleOpen access
  PublisherOA PDFDOI

• Frailty in Pediatric Liver Disease May Be Associated With an Increased Incidence of Readmissions After Pediatric Liver Transplantation

  Pediatric Transplantation · 2025-04-14 · 1 citations

  articleOpen access

  BACKGROUND: Frailty is a phenotype of cumulative decline leading to decreased physiologic reserve and vulnerability to stressors. Frailty is associated with adverse outcomes after liver transplantation (LT) in adults, but similar data are not available in children. A prospective multicenter study previously determined that frailty is present in 46% of children with end-stage liver disease (ESLD). We utilized this cohort to evaluate the impact of pre-transplant frailty on post-LT outcomes. METHODS: The study included pediatric participants from the original frailty study across 10 North American transplant centers who had subsequently undergone LT. Clinical outcomes were collected up to 1 year post LT. Participants were stratified by their pre-transplant frailty score (defined by a pre-LT frailty score of ≥ 6.0) and long-term outcomes were compared between groups. RESULTS: 28 (60.7% female, 46.4% biliary atresia) pediatric LT recipients were included, and 54% of children met criteria for frailty (n = 15). Baseline characteristics were comparable between groups; however, those with frailty were significantly more likely to have pre-transplant failure to thrive (33.3% vs. 0%, p = 0.044). Thirty-four hospital readmissions (22 in frail and 12 in non-frail children) occurred in 20 patients. Higher pre-transplant frailty scores were also significantly associated with an increased number of readmissions after transplantation (p = 0.034). CONCLUSIONS: Pediatric frailty may be associated with the adverse outcome of increased frequency of hospitalization in the first year after pediatric liver transplantation. These data support the concept that frail children should be identified and targeted for prehabilitation prior to LT.

  PublisherOA PDFDOI

• Condition-Specific Growth Charts for Children With Alagille Syndrome

  Utrecht University Repository (Utrecht University) · 2025-11-03

  articleOpen access

  IMPORTANCE: Different degrees of growth delay have been reported in children with Alagille syndrome (ALGS), yet these patients are routinely evaluated using standard growth charts. OBJECTIVE: To develop condition-specific growth charts for ALGS using modern statistical approaches. DESIGN, SETTING, AND PARTICIPANTS: This case series used data from the international, multicenter Global Alagille Alliance (GALA) study accrued between May 14, 2018, and March 20, 2023. Children born at full term between January 1, 1997, and August 31, 2019, with a clinically and/or genetically confirmed ALGS diagnosis and their native liver were included. Data from children with a known history of prematurity were excluded for the development of the growth charts. Data were analyzed from March 25, 2023, to December 30, 2024. EXPOSURE: Growth of children with Alagille syndrome. MAIN OUTCOMES AND MEASURES: Generalized additive models for location scale and shape were fitted to generate percentile plots for weight and height relative to age and superimposed on US Centers for Disease Control and Prevention (CDC) growth charts to illustrate differences in growth patterns compared with children with typical development. RESULTS: Data from 1204 children with ALGS in overlapping cohorts (median [IQR] gestational age, 38 [37-39] weeks) were analyzed (1204 in the weight cohort; 695 boys [57.7%]; 9855 weight observations; 995 with neonatal cholestasis [82.6%]; 306 receiving a liver transplant [25.4%]; 98 deaths [8.1%] and 1106 in the height cohort, 635 boys [57.4%]; 8464 height observations; 906 with neonatal cholestasis [81.9%]; 287 receiving a liver transplant [25.9%]; 86 deaths [7.8%]) were included for the modeling of the weight-for-age and height-for-age charts, respectively. The median birth weight was 2.8 kg (IQR, 2.5-3.0 kg) for boys and 2.6 kg (IQR, 2.4-2.9 kg) for girls. The median birth length was 48.0 cm (IQR, 46.0-50.0 cm) for boys and 47.0 cm (IQR, 45.0-49.0 cm) for girls. The weight-for-age and height-for-age growth charts for boys and girls with AGLS differed significantly from CDC growth charts. The estimated height at age 18 years corresponded to the 50th percentile was 171.5 cm for boys and 156.5 cm for girls on the condition-specific charts vs 176 cm and 163 cm, respectively, on the CDC growth charts. CONCLUSIONS AND RELEVANCE: These findings suggest that condition-specific growth charts for ALGS may provide a crucial tool for clinicians to evaluate growth and aid in decision-making around listing children for liver transplant.

  Publisher

Recent grants

• NIH Grant R01DK071841

  NIH · $1.8M · 2011

• NIH Grant R01DK090260

  NIH · $2.1M · 2017

• NIH Grant K08DK002796

  NIH · $647k · 2005

• Advancing our Understanding of Rare Pediatric Liver Diseases

  NIH · $8.8M · 2002–2029

Frequent coauthors

• Binita M. Kamath

  SickKids Foundation

  207 shared

• David A. Piccoli

  151 shared

• Nancy B. Spinner

  Children's Hospital of Philadelphia

  151 shared

• Saul J. Karpen

  Children's Healthcare of Atlanta

  143 shared

• Ronald J. Sokol

  University of Colorado Denver

  130 shared

• Vicky L. Ng

  Hospital for Sick Children

  121 shared

• Jean P. Molleston

  Riley Hospital for Children

  119 shared

• Philip Rosenthal

  University of California, San Francisco

  119 shared