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Successful response of primary sclerosing cholangitis and associated ulcerative colitis to oral vancomycin may depend on brand and personalized dose: report in an adolescent

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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 8 years. 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.

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References

  1. Lindor KD, Kowdley KV, Harrison ME, et al. ACG clinical guideline: primary sclerosing cholangitis. Am J Gastroenterol. 2015;110:646–59 (quiz 660).

    Article  CAS  Google Scholar 

  2. Miloh T, Arnon R, Shneider B, et al. A retrospective single-center review of primary sclerosing cholangitis in children. Clin Gastroenterol Hepatol. 2009;7:239–45.

    Article  Google Scholar 

  3. Feldstein AE, Perrault J, El-Youssif M, et al. Primary sclerosing cholangitis in children: a long-term follow-up study. Hepatology. 2003;38:210–7.

    Article  Google Scholar 

  4. Maroni L, Ninfole E, Pinto C, et al. Gut–liver axis and inflammasome activation in cholangiocyte pathophysiology. Cells. 2020;9:736. https://doi.org/10.3390/cells9030736.

    Article  CAS  Google Scholar 

  5. Laborda TJ, Jensen MK, Kavan M, et al. Treatment of primary sclerosing cholangitis in children. World J Hepatol. 2019;11:19–36.

    Article  Google Scholar 

  6. Olsson R, Boberg KM, de Muckadell OS, et al. High-dose ursodeoxycholic acid in primary sclerosing cholangitis: a 5-year multicenter, randomized, controlled study. Gastroenterology. 2005;129:1464–72.

    Article  CAS  Google Scholar 

  7. Lindor KD, Kowdley KV, Luketic VA, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. 2009;50:808–14.

    Article  CAS  Google Scholar 

  8. Tabibian JH, O’Hara SP, Lindor KD. Primary sclerosing cholangitis and the microbiota: current knowledge and perspectives on etiopathogenesis and emerging therapies. Scand J Gastroenterol. 2014;49:901–8.

    Article  Google Scholar 

  9. Shah A, Macdonald GA, Morrison M, et al. Targeting the gut microbiome as a treatment for primary sclerosing cholangitis: a conceptional framework. Am J Gastroenterol. 2020;115:814–22.

    Article  Google Scholar 

  10. Damman JL, Rodriguez EA, Ali AH, et al. Review article: the evidence that vancomycin is a therapeutic option for primary sclerosing cholangitis. Aliment Pharmacol Ther. 2018;47:886–95.

    Article  CAS  Google Scholar 

  11. Ali AH, Damman J, Shah SB, et al. Open-label prospective therapeutic clinical trials: oral vancomycin in children and adults with primary sclerosing cholangitis. Scand J Gastroenterol. 2020;55:941–50.

    Article  CAS  Google Scholar 

  12. Marcone GL, Binda E, Berini F, et al. Old and new glycopeptide antibiotics: from product to gene and back in the post-genomic era. Biotechnol Adv. 2018;36:534–54.

    Article  CAS  Google Scholar 

  13. Vesga O, Agudelo M, Salazar BE, et al. Generic vancomycin products fail in vivo despite being pharmaceutical equivalents of the innovator. Antimicrob Agents Chemother. 2010;54:3271–9.

    Article  CAS  Google Scholar 

  14. Louie A, Boyne MT, Patel V, et al. Pharmacodynamic evaluation of the activities of six parenteral vancomycin products available in the United States. Antimicrob Agents Chemother. 2015;59:622–32.

    Article  Google Scholar 

  15. Buness C, Lindor KD, Miloh T. Oral vancomycin therapy in a child with primary sclerosing cholangitis and severe ulcerative colitis. Pediatr Gastroenterol Hepatol Nutr. 2016;19:210–3.

    Article  Google Scholar 

  16. Buness JG, Ali AH, Tabibian JH, et al. Potential association of doxycycline with the onset of primary sclerosing cholangitis: a case series. Am J Ther. 2019. https://doi.org/10.1097/MJT.0000000000001065 ((published ahead of print)).

    Article  PubMed  Google Scholar 

  17. Bjornsson E, Olsson R, Bergquist A, et al. The natural history of small-duct primary sclerosing cholangitis. Gastroenterology. 2008;134:975–80.

    Article  Google Scholar 

  18. Davies YK, Cox KM, Abdullah BA, et al. Long-term treatment of primary sclerosing cholangitis in children with oral vancomycin: an immunomodulating antibiotic. J Pediatr Gastroenterol Nutr. 2008;47:61–7.

    Article  CAS  Google Scholar 

  19. Dean G, Hanauer S, Levitsky J. The role of the intestine in the pathogenesis of primary sclerosing cholangitis: evidence and therapeutic implications. Hepatology. 2020;72:1127–38.

    Article  Google Scholar 

  20. Tabibian JH, Weeding E, Jorgensen RA, et al. Randomised clinical trial: vancomycin or metronidazole in patients with primary sclerosing cholangitis—a pilot study. Aliment Pharmacol Ther. 2013;37:604–12.

    Article  CAS  Google Scholar 

  21. Davies YK, Tsay CJ, Caccamo DV, et al. Successful treatment of recurrent primary sclerosing cholangitis after orthotopic liver transplantation with oral vancomycin. Case Rep Transplant. 2013. https://doi.org/10.1155/2013/314292 ((publication ahead of print)).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Deneau MR. Oral vancomycin, ursodeoxycholic acid or no therapy for pediatric primary sclerosing cholangitis: a matched analysis. Hepatology. 2020. https://doi.org/10.1002/hep.31560 ((publication ahead of print)).

    Article  PubMed  Google Scholar 

  23. Siedlar M, Szczepanik A, Wiȩckiewicz J, et al. Vancomycin down-regulates lipopolysaccharide-induced tumour necrosis factor alpha (TNFα) production and TNFa-mRNA accumulation in human blood monocytes. Immunopharmacology. 1997;35:265–71.

    Article  CAS  Google Scholar 

  24. Abarbanel DN, Seki SM, Davies Y, et al. Immunomodulatory effect of vancomycin on Treg in pediatric inflammatory bowel disease and primary sclerosing cholangitis. J Clin Immunol. 2013;33:397–406.

    Article  CAS  Google Scholar 

  25. Nakamoto N, Sasaki N, Aoki R, et al. Gut pathobionts underlie intestinal barrier dysfunction and liver T helper 17 cell immune response in primary sclerosing cholangitis. Nat Microbiol. 2019;4:492–503.

    Article  CAS  Google Scholar 

  26. Vaughn BP, Kaiser T, Staley C, et al. A pilot study of fecal bile acid and microbiota profiles in inflammatory bowel disease and primary sclerosing cholangitis. Clin Exp Gastroenterol. 2019;12:9–19.

    Article  CAS  Google Scholar 

  27. Kim HK, Choi SM, Kang G, et al. Comparison of in vivo pharmacokinetics and pharmacodynamics of vancomycin products available in Korea. Yonsei Med J. 2020;61:301–9.

    Article  CAS  Google Scholar 

  28. Sauter M, Uhl P, Meid AD, et al. New insights into the pharmacokinetics of vancomycin after oral and intravenous administration: an investigation in beagle dogs. J Pharm Sci. 2020;109:2090–4.

    Article  CAS  Google Scholar 

  29. FDA Advisory Committee meeting and ViroPharma letter, 2009. https://www.wayback.archive-it.org/7993/20170405230228. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AdvisoryCommitteeforPharmaceuticalScienceandClinicalPharmacology/UCM175010.pdf . Accessed 12 Sept 2020.

  30. Serai SD, Obuchowski NA, Venkatesh SK, et al. Repeatability of MR elastography of liver: a meta-analysis. Radiology. 2017;217:92–100.

    Article  Google Scholar 

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Authors and Affiliations

  1. National Patient Advocate Foundation, Arizona State University, Phoenix, AZ, USA

    Cynthia W. Buness

  2. Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA

    Kevin M. Johnson

  3. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA

    Ahmad Hassan Ali

  4. Division of Pediatric Gastroenterology, Hepatology and Nutrition, Stanford University, Palo Alto, CA, USA

    Leina Alrabadi

  5. Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ, USA

    Keith D. Lindor

  6. Miami Transplant Institute, 1801 NW 9th Avenue, Miami, FL, USA

    Tamir Miloh

  7. Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Stanford University, Palo Alto, CA, USA

    Kenneth L. Cox

  8. Emeritus Professor of Pediatrics, Stanford University, Palo Alto, CA, USA

    Kenneth L. Cox

Authors
  1. Cynthia W. Buness
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  2. Kevin M. Johnson
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  3. Ahmad Hassan Ali
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  4. Leina Alrabadi
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  5. Keith D. Lindor
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  6. Tamir Miloh
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  7. Kenneth L. Cox
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Corresponding author

Correspondence to Kenneth L. Cox.

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Conflict of interest

Cynthia W. Buness, Kevin M. Johnson, Ahmad Hassan Ali, Leina Alrabadi, Keith D. Lindor, Tamir Miloh, and Kenneth L. Cox, M.D. all declare that they have no conflict of interest.

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All procedures followed have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Informed consent was obtained from the patient for being included in the study.

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Buness, C.W., Johnson, K.M., Ali, A.H. et al. Successful response of primary sclerosing cholangitis and associated ulcerative colitis to oral vancomycin may depend on brand and personalized dose: report in an adolescent. Clin J Gastroenterol 14, 684–689 (2021). https://doi.org/10.1007/s12328-020-01296-0

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  • DOI: https://doi.org/10.1007/s12328-020-01296-0

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