Leina Alrabadi

All Publications

• A-LINK: UTILIZING A LEARNING HEALTH NETWORK MODEL FOR IMPROVING OUTCOMES IN AUTOIMMUNE HEPATITIS Taylor, A. E., Castro-Rojas, C., Karns, R., Mudaliar, K., Moor, M., Alquraish, M., Kulkarni, S., Gupta, N., Alrabadi, L., Halma, J., Bhatt, H., Saarela, K., Ayers, M., Saeed, S., Squires, J. E., Miethke, A. G. LIPPINCOTT WILLIAMS & WILKINS. 2023: S117-S118

  View details for Web of Science ID 001094865400118

• Letter to the Editor: Insurance should cover vancomycin for primary sclerosing cholangitis. Hepatology (Baltimore, Md.) Ali, A. H., Buness, C. W., Fischer, R., Holtmann, G. J., Shah, A., Lewindon, P., Shah, S., Ragnekar, A. S., Taylor, A. E., Goel, A., Cox, K. L., Alrabadi, L., Wadsworth, S., Kulkarni, S. S., Lindor, K. D. 2023

  View details for DOI 10.1097/HEP.0000000000000304

  View details for PubMedID 36705026

• Mindfulness-based stress reduction may decrease stress, disease activity, and inflammatory cytokine levels in patients with autoimmune hepatitis. JHEP reports : innovation in hepatology Alrabadi, L. S., Dutton, A., Rabiee, A., Roberts, S. J., Deng, Y., Cusack, L., Silveira, M. G., Ciarleglio, M., Bucala, R., Sinha, R., Boyer, J. L., Assis, D. N. 2022; 4 (5): 100450

  Abstract

  Background & Aims: Psychological and life stressors may impact autoimmune hepatitis (AIH) disease activity and increase relapse risk. Mindfulness-based stress reduction (MBSR) is a validated course that reduces stress reactivity, and improves stress and emotion regulation. This single-arm exploratory pilot study of adult patients with AIH aimed to define the impact of an 8-week MBSR program on quality of life, disease activity, and cytokine mediators.Methods: The perceived stress survey-10 (PSS) and the brief self-control scale (BSCS) measured subjective distress and self-control. Serum alanine aminotransferase (ALT) and cytokine levels were measured, and immunosuppressant doses recorded.Results: Seventeen patients completed the MBSR program. Post-MBSR, 71% (n = 12) showed PSS score improvement at 8 weeks vs. baseline (median 15 vs. 21, p = 0.02). At 12 months, PSS improvement persisted vs. baseline (median 15 vs. 21, p = 0.02). Post-MBSR, 71% (n = 12) showed BSCS score improvement at 8 weeks vs. baseline (median 4.1 vs. 3.8, p = 0.03). At 12 months, the median BSCS score remained significant (3.9 vs. 3.8, p = 0.03). After the 8-week MBSR, the 35% of patients with ALT >34 U/L had a median ALT reduction (44.5 vs. 71.5 U/L, p = 0.06), whereas the 71% of patients on prednisone had significant dose reductions (5.75 vs. 10 mg, p = 0.02) which persisted at 12 months vs. baseline (3.75 vs. 10 mg, p = 0.02) without a compensatory increase in steroid-sparing dosing. Significant improvement was noted in peripheral blood cytokine levels (IL-6, IL-8, IL-10, IL-17, IL-23, and sCD74/MIF ratio) from baseline to 8 weeks.Conclusions: MBSR significantly improved perceived stress and self-control scores while decreasing ALT levels, steroid requirements, and inflammatory cytokine levels in this pilot study in adult AIH. Stress modification may impact quality of life and disease activity, and should be further evaluated as an intervention in AIH.Clinical Trials registration: This study is registered at ClinicalTrials.gov (NCT02950077).Lay summary: Autoimmune hepatitis can reduce quality of life and mental health, while stress may impact autoimmune hepatitis itself. We piloted mindfulness-based stress reduction as a strategy to reduce stress in adult patients with autoimmune hepatitis and found that the intervention reduced perceived stress and may have also impacted the disease by improving inflammation and medication needs. Stress reduction should be further studied to improve quality of life and possibly to impact disease activity in autoimmune hepatitis.

  View details for DOI 10.1016/j.jhepr.2022.100450

  View details for PubMedID 35434588

• Global multi-stakeholder endorsement of the MAFLD definition. The lancet. Gastroenterology & hepatology Méndez-Sánchez, N., Bugianesi, E., Gish, R. G., Lammert, F., Tilg, H., Nguyen, M. H., Sarin, S. K., Fabrellas, N., Zelber-Sagi, S., Fan, J. G., Shiha, G., Targher, G., Zheng, M. H., Chan, W. K., Vinker, S., Kawaguchi, T., Castera, L., Yilmaz, Y., Korenjak, M., Spearman, C. W., Ungan, M., Palmer, M., El-Shabrawi, M., Gruss, H. J., Dufour, J. F., Dhawan, A., Wedemeyer, H., George, J., Valenti, L., Fouad, Y., Romero-Gomez, M., Eslam, M. 2022

  View details for DOI 10.1016/S2468-1253(22)00062-0

  View details for PubMedID 35248211

• THE IMPACT OF SARS-COV2 INFECTION IN CHILDREN WITH LIVER DISEASE: AN INTERNATIONAL OBSERVATIONAL REGISTRY STUDY Kehar, M., Ebel, N. H., Ng, V., Sehgal, A., Slowik, V., Leung, D. H., Shah, A. A., Ovchinsky, N., Kogan-Liberman, D., Arnon, R., Vitola, B., Waheed, N., Lebel, S., Mohammad, S., Squires, J. E., Shteyer, E., Miloh, T. A., Sanchez, M., Hildreth, A., Yerushalmi, B. Y., Chu, C., Kader, H., Book, L., Alrabadi, L., Zheng, M., Namjoshi, S. S., Cagil, Y., Fuchs, Y., Lobritto, S. J., Martinez, M. WILEY. 2021: 1180A-1181A

  View details for Web of Science ID 000707188005343

• THE IMPACT OF SARS-CoV2 INFECTION IN PEDIATRIC LIVER TRANSPLANT RECIPIENTS: AN INTERNATIONAL OBSERVATIONAL REGISTRY STUDY Ebel, N. H., Kehar, M., Ng, V., Sehgal, A., Leung, D. H., Shah, A. A., Gupta, N., Baqueros, J., Botha, J., Slowik, V., Lebel, S., Miloh, T. A., Shteyer, E., Arnon, R., Azzam, R. K., Ovchinsky, N., Mohammad, S., Kogan-Liberman, D., Squires, J. E., Sanchez, M., Hildreth, A., Book, L., Chu, C., Alrabadi, L., Chepuri, B., D'Agostino, D., Elisofon, S., Falik, R., Gallagher, L., Kader, H., Lam, S., Mogul, D., Mujawar, Q., Namjoshi, S. S., Valentino, P. L., Vitola, B., Waheed, N., Zheng, M., Blondet, N., Lobritto, S. J., Martinez, M. WILEY. 2021: 136A-137A

  View details for Web of Science ID 000707188000205

• Letter to the editor: Oral vancomycin versus no therapy for pediatric primary sclerosing cholangitis. Hepatology (Baltimore, Md.) Johnson, K. M., Fischer, R. T., Holtmann, G. J., Shah, A., Alrabadi, L., Lewindon, P. 2021

  Abstract

  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).

  View details for DOI 10.1002/hep.31764

  View details for PubMedID 33638221

• SARS-CoV2 Infection in Children with Liver Transplant and Native Liver Disease: An International Observational Registry Study. Journal of pediatric gastroenterology and nutrition Kehar, M. n., Ebel, N. H., Ng, V. L., Baquero, J. E., Leung, D. H., Slowik, V. n., Ovchinsky, N. n., Shah, A. A., Arnon, R. n., Miloh, T. n., Gupta, N. n., Mohammad, S. n., Kogan-Liberman, D. n., Squires, J. E., Sanchez, M. C., Hildreth, A. n., Book, L. n., Chu, C. n., Alrabadi, L. n., Azzam, R. n., Chepuri, B. n., Falik, R. n., Gallagher, L. n., Kader, H. n., Mogul, D. n., Mujawar, Q. n., Namjoshi, S. S., Valentino, P. L., Vitola, B. n., Waheed, N. n., Zheng, M. H., Lobritto, S. n., Martinez, M. n. 2021

  Abstract

  Increased mortality risk due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection in adults with native liver disease (LD) and liver transplant (LT) is associated with advanced age and comorbid conditions. We aim to report outcomes for children with LD and LT enrolled in the NASPGHAN/SPLIT SARS-CoV2 registry.In this multicenter observational cohort study, we collected data from 91 patients <21 years (LD 44, LT 47) with laboratory-confirmed SARS-CoV2 infection between April 21 and September 17, 2020.Patients with LD were more likely to require admission (70% vs 43% LT, p = 0.007) and pediatric intensive care unit (PICU) management (32% vs 4% LT, p = 0.001). Seven LD patients required mechanical ventilation (MV) and 2 patients died; no patients in the LT cohort died or required MV. Four LD patients presented in pediatric acute liver failure (PALF), 2 with concurrent multisystem inflammatory syndrome in children (MIS-C); all recovered without LT. Two LD patients had MIS-C alone and one patient died. Bivariable logistic-regression analysis found that patients with non-alcoholic fatty liver disease (NAFLD) (OR 5.6, p = 0.02) and LD (OR 6.1, p = 0.01, vs LT) had higher odds of severe disease (PICU, vasopressor support, MV, renal replacement therapy or death).Although not directly comparable, LT recipients had lower odds of severe SARS-CoV2 infection (vs LD), despite immunosuppression burden. NAFLD patients reported to the registry had higher odds of severe SARS-CoV2 disease. Future controlled studies are needed to evaluate effective treatments and further stratify LD and LT patients with SARS-CoV2 infection.

  View details for DOI 10.1097/MPG.0000000000003077

  View details for PubMedID 33605666

• Successful response of primary sclerosing cholangitis and associated ulcerative colitis to oral vancomycin may depend on brand and personalized dose: report in an adolescent. Clinical journal of gastroenterology Buness, C. W., Johnson, K. M., Ali, A. H., Alrabadi, L., Lindor, K. D., Miloh, T., Cox, K. L. 2020

  Abstract

  Primary sclerosing cholangitis (PSC) is a rare, progressive liver disease characterized by cholestasis and bile duct fibrosis that has no accepted therapy known to delay or arrest its progression. We report a 23-year-old female patient who at age 14 was diagnosed with moderate pancolonic ulcerative colitis (UC) and at age 15 with small-duct PSC unresponsive to conventional therapy. The patient began single drug therapy with the antibiotic oral vancomycin (OVT) and achieved normalization of liver enzymes and resolution of UC symptoms with colonic mucosal healing. These improvements have persisted over 8years. There has been no colon dysplasia, liver fibrosis or failure, bile duct stricture, or cancer. Of note, the patient's response was dependent on the brand of oral vancomycin capsule, as well as dose. This raised the questions of possible differences in bioequivalence of different commercial versions of the drug and whether this factor might play into the variability of efficacy seen in published trials. Evidence suggests that oral vancomycin both alters the intestinal microbiome and has immunomodulatory effects. Its striking effectiveness in this and other patients supports further investigation in randomized trials, with careful attention to its bioavailability profile in the gut.

  View details for DOI 10.1007/s12328-020-01296-0

  View details for PubMedID 33231850

• Open-label prospective therapeutic clinical trials: oral vancomycin in children and adults with primary sclerosing cholangitis. Scandinavian journal of gastroenterology Ali, A. H., Damman, J., Shah, S. B., Davies, Y., Hurwitz, M., Stephen, M., Lemos, L. M., Carey, E. J., Lindor, K. D., Buness, C. W., Alrabadi, L., Berquist, W. E., Cox, K. L. 2020: 1–10

  Abstract

  BACKGROUND: Oral vancomycin (OV) in primary sclerosing cholangitis (PSC) has been evaluated as a potential therapeutic agent. We report the long-term biochemical course and outcomes of patients with PSC treated with OV.METHODS: Patients were enrolled in 2 open-label clinical trials (ClinicalTrials.gov Identifier: NCT01802073 and NCT01322386) and offered OV at 50mg/kg/day in 3 divided doses if weight <30kg, and 500mg 3 times/day if weight ≥30kg. Patients with biliary strictures requiring stenting or awaiting liver transplant were excluded. Liver biochemistry, MRCP and histology were documented at baseline and while on OV. The primary outcome was a decrease in elevated gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), and/or alanine aminotransferase (ALT) from baseline.RESULTS: 30 subjects were enrolled, and 29 additional subjects who learned of the clinical trial requested OV (total n=59; median age was 13.5years [range, 1.5-44years]; 64.4% were male; and 94.9% had inflammatory bowel disease [IBD]). The median treatment duration was 2.7years (range, 0.2-14years). Ninety-six percent (57/59), 81.3% (48/59), and 94.9% (56/59) experienced reduction of GGT, ALP, and ALT, respectively. Furthermore, 39% (23/59), 22% (13/59), and 55.9% (33/59) experienced normalization of GGT, ALP, and ALT, respectively, within the first 6months of OV treatment. One patient underwent liver transplantation 8years after beginning OV treatment, and one developed biliary strictures requiring endoscopic intervention. OV was well-tolerated by patients, and no patient developed treatment-related adverse events.CONCLUSION: In PSC, OV was well-tolerated and was associated with improvement in liver chemistry. A randomized placebo-controlled clinical trial is warranted.

  View details for DOI 10.1080/00365521.2020.1787501

  View details for PubMedID 32633158

• Bile-Derived Organoids From Patients With Primary Sclerosing Cholangitis Recapitulate Their Inflammatory Immune Profile. Hepatology (Baltimore, Md.) Soroka, C. J., Assis, D. N., Alrabadi, L. S., Roberts, S., Cusack, L., Jaffe, A. B., Boyer, J. L. 2019; 70 (3): 871–82

  Abstract

  Primary sclerosing cholangitis (PSC) is a heterogeneous and progressive fibroinflammatory cholangiopathy with no known etiology or effective treatment. Studies of PSC are limited due to difficulty in accessing the cholangiocyte, the small percentage of these cells in the liver, instability of in vitro culture systems, and reliance on samples from end-stage disease. Here, we demonstrate that stem cells can be isolated from the bile of PSC patients undergoing endoscopic retrograde cholangiopancreatography earlier in their clinical course and maintained long term in vitro as three-dimensional (3D) organoids that express a biliary genetic phenotype. Additionally, bile-derived organoids (BDOs) can be biobanked and samples obtained longitudinally over the course of the disease. These BDOs express known cholangiocyte markers including gamma glutamyl transferase, cytokeratin 19, epithelial cellular adhesion molecule, cystic fibrosis transmembrane conductance regulator, and anion exchanger 2. RNA sequence analysis identified 39 genes whose expression differed in organoids from PSC patients compared to non-PSC controls, including human leukocyte antigen DM alpha chain and chemokine (C-C motif) ligand 20 (CCL20), immune-related genes previously described in genome-wide association studies of PSC. Incubation of these BDOs with interleukin 17A or tumor necrosis factor alpha led to an immune-reactive phenotype with a significant increase in secretion of proinflammatory mediators, including CCL20, a T-cell chemoattractant. Conclusion: This study demonstrates that bile can be used as a source of biliary-like cells that can be maintained long term in vitro as 3D organoids; these BDOs retain features of cholangiopathies, including the ability to react to inflammatory stimuli by secreting chemokines and propagating an immune-reactive phenotype reflective of the pathogenesis of these diseases; thus, BDOs represent a platform for the study of the pathogenesis and therapy of cholangiopathies, particularly PSC.

  View details for DOI 10.1002/hep.30470

  View details for PubMedID 30561836

• Refractory Infantile Chronic Diarrhea and Failure to Thrive in a 6-Month-Old Boy With a Complex Past Medical History CLINICAL PEDIATRICS Okafor, D., AlRabadi, L., Alper, A., Jeffries, L., McGrath, J., Porto, A. F. 2019; 58 (6): 707–10

  View details for DOI 10.1177/0009922819832034

  View details for Web of Science ID 000466124900017

  View details for PubMedID 30788983

• Bile-Derived Organoids from PSC Patients Recapitulate the Inflammatory Immune Profile Seen in Cholangiopathies, Providing an in Vitro Model to Test Candidate Therapeutic Agents. Soroka, C. J., Assis, D. N., Alrabadi, L., Roberts, S., Cusack, L., Silveira, M. G., Boyer, J. L. WILEY. 2018: 1080A

  View details for Web of Science ID 000446020503126

• Mindfulness-Based Stress Reduction Improves Stress, Disease Activity and Cytokine Levels in Patients with Autoimmune Hepatitis (AIH) Alrabadi, L., Dutton, A., Roberts, S., Deng, Y., Cusack, L., Rabiee, A., Silveira, M. G., Ciarleglio, M., Sinha, R., Assis, D. N., Boyer, J. L. WILEY. 2018: 1119A–1120A

  View details for Web of Science ID 000446020503191

• Assessment of Community Pediatric Providers' Approach to a Child With Celiac Disease and Available Serological Testing Associated With a Large Tertiary Care Center CLINICAL PEDIATRICS Alrabadi, L. S., Porto, A. F. 2018; 57 (10): 1199–1203

  Abstract

  An evidence-practice gap for use of celiac disease testing can lead to poor resource utilization. False positive tests may lead to unnecessary diet changes, gastroenterology consults, parental/patient concern, and additional testing and expenses complicated by varied available celiac bundles. An understanding of pediatric provider practices according to guideline recommendations further improves this gap.

  View details for DOI 10.1177/0009922818769453

  View details for Web of Science ID 000440685200009

  View details for PubMedID 29667919

• Biliary drainage as treatment for allograft steatosis following liver transplantation for PFIC-1 disease: A single-center experience PEDIATRIC TRANSPLANTATION Alrabadi, L. S., Morotti, R. A., Valentino, P. L., Rodriguez-Davalos, M. I., Ekong, U. D., Emre, S. H. 2018; 22 (4): e13184

  Abstract

  Development of macrovesicular steatosis post-LT in patients with PFIC-1 is increasingly being observed, with the etiology not fully understood. We highlight successful and effective EBD for reversal of allograft steatosis in 2 patients with PFIC-1 disease and discuss our experience with internal biliary diversion in this patient population.

  View details for DOI 10.1111/petr.13184

  View details for Web of Science ID 000433590800014

  View details for PubMedID 29654655

• Human bile contains stem cells which can be cultured in vitro as 3D organoids. Soroka, C. J., Alrabadi, L., Mennone, A., Assis, D. N., Rodriguez, R., Boyer, J. L. WILEY. 2017: 64A

  View details for Web of Science ID 000412089800110

• Diet-Induced Obesity Promotes Colon Tumor Development in Azoxymethane-Treated Mice PLOS ONE Tuominen, I., Al-Rabadi, L., Stavrakis, D., Karagiannides, I., Pothoulakis, C., Bugni, J. M. 2013; 8 (4): e60939

  Abstract

  Obesity is an important risk factor for colon cancer in humans, and numerous studies have shown that a high fat diet enhances colon cancer development. As both increased adiposity and high fat diet can promote tumorigenesis, we examined the effect of diet-induced obesity, without ongoing high fat diet, on colon tumor development. C57BL/6J male mice were fed regular chow or high fat diet for 8 weeks. Diets were either maintained or switched resulting in four experimental groups: regular chow (R), high fat diet (H), regular chow switched to high fat diet (RH), and high fat diet switched to regular chow (HR). Mice were then administered azoxymethane to induce colon tumors. Tumor incidence and multiplicity were dramatically smaller in the R group relative to all groups that received high fat diet at any point. The effect of obesity on colon tumors could not be explained by differences in aberrant crypt foci number. Moreover, diet did not alter colonic expression of pro-inflammatory cytokines tumor necrosis factor-α, interleukin-6, interleukin-1β, and interferon-γ, which were measured immediately after azoxymethane treatment. Crypt apoptosis and proliferation, which were measured at the same time, were increased in the HR relative to all other groups. Our results suggest that factors associated with obesity - independently of ongoing high fat diet and obesity - promote tumor development because HR group animals had significantly more tumors than R group, and these mice were fed the same regular chow throughout the entire carcinogenic period. Moreover, there was no difference in the number of aberrant crypt foci between these groups, and thus the effect of obesity appears to be on subsequent stages of tumor development when early preneoplastic lesions transition into adenomas.

  View details for DOI 10.1371/journal.pone.0060939

  View details for Web of Science ID 000318840100109

  View details for PubMedID 23560112

  View details for PubMedCentralID PMC3616169

• The neurotensin receptor-1 promotes tumor development in a sporadic but not an inflammation-associated mouse model of colon cancer INTERNATIONAL JOURNAL OF CANCER Bugni, J. M., Al-Rabadi, L., Jubbal, K., Karagiannides, I., Lawson, G., Pothoulakis, C. 2012; 130 (8): 1798–1805

  Abstract

  Neurotensin receptor-1 (NTR-1) is overexpressed in colon cancers and colon cancer cell lines. Signaling through this receptor stimulates proliferation of colonocyte-derived cell lines and promotes inflammation and mucosal healing in animal models of colitis. Given the causal role of this signaling pathway in mediating colitis and the importance of inflammation in cancer development, we tested the effects of NTR-1 in mouse models of inflammation-associated and sporadic colon cancer using NTR-1-deficient (Ntsr1(-) (/-)) and wild-type (Ntsr1(+/+)) mice. In mice treated with azoxymethane (AOM) to model sporadic cancer, NTR-1 had a significant effect on tumor development with Ntsr1(+/+) mice developing over twofold more tumors than Ntsr1(-) (/-) mice (p = 0.04). There was no effect of NTR-1 on the number of aberrant crypt foci or tumor size, suggesting that NT/NTR-1 signaling promotes the conversion of precancerous cells to adenomas. Interestingly, NTR-1 status did not affect tumor development in an inflammation-associated cancer model where mice were treated with AOM followed by two cycles of 5% dextran sulfate sodium (DSS). In addition, colonic molecular and histopathologic analyses were performed shortly after a single cycle of DSS. NTR-1 status did not affect colonic myeloperoxidase activity or histopathologic scores for damage and inflammation. However, Ntsr1(-) (/-) mice were more resistant to DSS-induced mortality (p = 0.01) and had over twofold higher colonic expression levels of Il6 and Cxcl2 (p < 0.04), cytokines known to promote tumor development. These results represent the first direct demonstration that targeted disruption of the Ntsr1 gene reduces susceptibility to colon tumorigenesis.

  View details for DOI 10.1002/ijc.26208

  View details for Web of Science ID 000300692300009

  View details for PubMedID 21630261

  View details for PubMedCentralID PMC3288327

• Obesity in the Absence of High Fat Diet Enhances Tumor Development in AOM-Treated Mice Bugni, J. M., Al Rabadi, L., Stavrakis, D. G., Jubbal, K., Karagiannidis, I., Pothoulakis, C. W B SAUNDERS CO-ELSEVIER INC. 2011: S818

  View details for Web of Science ID 000290167303612