Alagille Syndrome Research and Outcomes

As a part of Stanford Medicine, our physician-scientists lead investigations into the fundamental biology, diagnoses, and care of the heart and liver disease associated with Alagille syndrome. We harness “big data” gathered from patients across the continuum of care to advance understanding of pathological processes with the fundamental goal of improving patient care. Our research reveals novel discoveries about Alagille syndrome. We were the first to describe the general pattern of pulmonary artery involvement in Alagille syndrome and demonstrated how computer simulations can assist in determining the best surgical options.

Our research leads to new and improved treatments and surgeries for children with Alagille syndrome. We’ve pushed the envelope with clinical innovations for the surgical management of complex pulmonary artery anomalies related to Alagille syndrome, including unifocalization. Dr. Frank Hanley, with our Alagille program and also the PAR program, has conducted more than 1,000 unifocalization procedures for tetralogy of Fallot since inventing this innovative marathon surgery that rolls several procedures into one.

Published research

Listed below are some of the articles written by Stanford team members about Alagille syndrome or the novel unifocalization procedure:

1. Outcomes in Patients with Alagille Syndrome and Complex Pulmonary Artery Disease.
   Luong R, Feinstein JA, Ma M, Ebel NH, Wise-Faberowski L, Zhang Y, Peng LF, Yarlagadda VV, Shek J, Hanley FL, McElhinney DB. J Pediatr. 2020 Sep 24:S0022-3476(20)31245-2. doi: 10.1016/j.jpeds.2020.09.053. Epub ahead of print. PMID: 32980376

2. Surgical Repair of Peripheral Pulmonary Artery Stenosis in Patients Without Williams or Alagille Syndromes.
   Martin E, Mainwaring RD, Collins RT 2nd, MacMillen KL, Hanley FL. Semin Thorac Cardiovasc Surg. 2020 Jan 17:S1043-0679(20)30003-4. doi: 10.1053/j.semtcvs.2020.01.003. Online ahead of print. PMID: 31958550

3. Pulmonary Hemorrhage in Children With Alagille Syndrome Undergoing Cardiac Catheterization.
   Adamson GT, Peng LF, Feinstein JA, Yarlagadda VV, Lin A, Wise-Faberowski L, McElhinney DB. Catheter Cardiovasc Interv. 2020 Feb;95(2):262–69. doi: 10.1002/ccd.28508. Epub 2019 Oct 4. PMID: 31584246

4. Outcomes After Initial Unifocalization to a Shunt in Complex Tetralogy of Fallot With MAPCAs.
   Bauser-Heaton H, Ma M, Wise-Faberowski L, Asija R, Shek J, Zhang Y, Peng LF, Sidell DR, Hanley FL, McElhinney DB. Ann Thorac Surg. 2019 Jun;107(6):1807–15. doi: 10.1016/j.athoracsur.2019.01.030. Epub 2019 Feb 14. PMID: 30772338

5. Syndromes With Aortic Involvement: Pictorial Review.
   Zucker EJ. Cardiovasc Diagn Ther. 2018 Apr;8(Suppl 1):S71–S81. doi: 10.21037/cdt.2017.09.14.PMID: 29850420 Free PMC article. Review.

6. Computational Simulation of Postoperative Pulmonary Flow Distribution in Alagille Patients With Peripheral Pulmonary Artery Stenosis.
   Yang W, Hanley FL, Chan FP, Marsden AL, Vignon-Clementel IE, Feinstein JA. Congenit Heart Dis. 2018 Mar;13(2):241–50. doi: 10.1111/chd.12556. Epub 2017 Dec 1. PMID: 29194961

7. Human Hepatic Organoids for the Analysis of Human Genetic Diseases.
   Guan Y, Xu D, Garfin PM, Ehmer U, Hurwitz M, Enns G, Michie S, Wu M, Zheng M, Nishimura T, Sage J, Peltz G. JCI Insight. 2017 Sep 7;2(17):e94954. doi: 10.1172/jci.insight.94954. eCollection 2017 Sep 7. PMID: 28878125 Free PMC article.

8. Surgical Techniques for Repair of Peripheral Pulmonary Artery Stenosis.
   Mainwaring RD, Hanley FL. Semin Thorac Cardiovasc Surg. 2017 Summer;29(2):198–205. doi: 10.1053/j.semtcvs.2017.05.001. Epub 2017 May 17. PMID: 28823329

9. Development of a Novel Tool to Assess the Impact of Itching in Pediatric Cholestasis.
   Kamath BM, Abetz-Webb L, Kennedy C, Hepburn B, Gauthier M, Johnson N, Medendorp S, Dorenbaum A, Todorova L, Shneider BL. Patient. 2018 Feb;11(1):69–82. doi: 10.1007/s40271-017-0266-4. PMID: 28710680. Free PMC article.

10. Programmatic Approach to Management of Tetralogy of Fallot With Major Aortopulmonary Collateral Arteries: A 15-Year Experience With 458 Patients.
    Bauser-Heaton H, Borquez A, Han B, Ladd M, Asija R, Downey L, Koth A, Algaze CA, Wise-Faberowski L, Perry SB, Shin A, Peng LF, Hanley FL, McElhinney DB. Circ Cardiovasc Interv. 2017 Apr;10(4):e004952. doi: 10.1161/CIRCINTERVENTIONS.116.004952. PMID: 28356265. Clinical trial.

11. Surgical Techniques for Repair of Peripheral Pulmonary Artery Stenosis.
    Mainwaring RD, Hanley FL. Semin Thorac Cardiovasc Surg. 2016 Summer;28(2):418–24. doi: 10.1053/j.semtcvs.2016.07.003. Epub 2016 Jul 18. PMID: 28043454

12. CT-defined phenotype of pulmonary artery stenoses in Alagille syndrome.
    Rodriguez RM, Feinstein JA, Chan FP. Pediatr Radiol. 2016 Jul;46(8):1120–27. doi: 10.1007/s00247-016-3580-4. Epub 2016 Apr 4. PMID: 27041277

13. Surgical Reconstruction of Peripheral Pulmonary Artery Stenosis in Williams and Alagille Syndromes.
    Monge MC, Mainwaring RD, Sheikh AY, Punn R, Reddy VM, Hanley FL. J Thorac Cardiovasc Surg. 2013 Feb;145(2):476–81. doi: 10.1016/j.jtcvs.2012.09.102. Epub 2012 Dec 8. PMID: 23228407

14. Atherosclerosis Causing Recurrent Catastrophic Aortopulmonary Shunt Dehiscence in a Patient With Alagille Syndrome.
    May L, Hanley FL, Connolly AJ, Reddy S. Pediatr Cardiol. 2013;34(8):1945–48. doi: 10.1007/s00246-012-0484-4. Epub 2012 Aug 26. PMID: 22923029

15. Surgical Outcomes for Patients With Pulmonary Atresia/Major Aortopulmonary Collaterals and Alagille Syndrome.
    Mainwaring RD, Sheikh AY, Punn R, Reddy VM, Hanley FL. Eur J Cardiothorac Surg. 2012 Aug;42(2):235–40; discussion 240–1. doi: 10.1093/ejcts/ezr310. Epub 2012 Mar 7. PMID: 22402453

16. SIR 2008 Annual Meeting Film Panel Case: Alagille Syndrome.
    Sze DY, Esquivel CO. J Vasc Interv Radiol. 2008 Sep;19(9):1278–80. doi: 10.1016/j.jvir.2008.04.016. Epub 2008 Jun 6. PMID: 18725089. No abstract available.

17. Moyamoya Syndrome in Children With Alagille Syndrome: Additional Evidence of a Vasculopathy.
    Woolfenden AR, Albers GW, Steinberg GK, Hahn JS, Johnston DC, Farrell K. Pediatrics. 1999 Feb;103(2):505–8. doi: 10.1542/peds.103.2.505. PMID: 9925853. No abstract available.

Other related research

• Cardiac, Aortic, and Pulmonary Vascular Involvement in Alagille Syndrome
• Reperfusion Pulmonary Edema in Children With Tetralogy of Fallot, Pulmonary Atresia, and Major Aortopulmonary Collateral Arteries Undergoing Unifocalization Procedures: A Pilot Study Examining Potential Pathophysiologic Mechanisms and Clinical Significance
• Early and Intermediate Outcomes After Repair of Pulmonary Atresia With Ventricular Septal Defect and Major Aortopulmonary Collateral Arteries: Experience With 85 Patients
• Early Complete Repair of Pulmonary Atresia With Ventricular Septal Defect and Major Aortopulmonary Collaterals

Outcomes

• Our Betty Irene Moore Children’s Hospital Heart Center team has cared for children from 49 U.S. states and 18 foreign countries to date. We consistently rank as one of the top pediatric cardiac programs in the nation when it comes to the volume of heart surgeries we perform at Stanford Medicine Children’s Health. Our unparalleled heart surgery outcomes include an overall non-risk-adjusted survival rate that’s greater than 97 percent, which is exceptional given the high-complexity and high-risk patients who are referred to us from around the world.
• Stanford Medicine Children’s Health’s pediatric liver transplant team is a national liver transplant volume leader, and our three-year liver graft patient survival rates are the best in the country.