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Progressive Cholestasis and Biliary Cirrhosis After Initiating Oral Semaglutide: Report From the Drug-Induced Liver Injury Network

Ma, Jiayi, Mathur, Karan, Muldoon, Jessica L., Ghabril, Marwan, Chalasani, Naga, Vuppalanchi, Raj·2022·ACG Case Reports Journal

Abstract

Semaglutide has little hepatic metabolism and is deemed low risk for causing drug-induced liver injury (DILI). We present a case of DILI from the US DILI Network. The case involved a 51-year-old man with type 2 diabetes who presented with jaundice and acute-on-chronic kidney disease 6 months after starting oral semaglutide. His liver injury progressed to biliary cirrhosis, accompanied by nephritis that led to end-stage renal disease. Extensive evaluations including liver and kidney biopsies revealed no alternative etiologies. Cholestatic gene sequencing revealed heterozygosity for ABCC2 and DHCR7 . He eventually underwent combined liver and kidney transplantation.

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Crossref · 10.14309/crj.0000000000000922

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Figures

Figure 1. Clinical course, trends in liver biochemistries over time as it relates to initiation of oral semaglutide, discontinuation, liver and kidney biopsy, and finally simultaneous liver and kidney transplantation.
Figure 1. Clinical course, trends in liver biochemistries over time as it relates to initiation of oral semaglutide, discontinuation, liver and kidney biopsy, and finally simultaneous liver and kidney transplantation.CC BY-NC-ND · PubMed Central
Figure 2. (A) Liver (×40, hematoxylin and eosin [H&E] stain): Largely preserved hepatic architecture with focal hepatocyte ballooning and marked and diffuse bile duct injury. (B) Liver (×200, H&E): Marked bile duct injury with mild to focally moderate inflammatory infiltrate consisting of lymphocytes and rare plasma cells. Hepatocyte ballooning (arrow). (C) Liver (×400, H&E): Mild cholestasis (arrow, circle). (D) Kidney (×400, H&E): Interstitial inflammatory infiltrate, including eosinophils (arrow), are present within a background of tubular atrophy (star). Extravasated red blood cells are seen on the right.
Figure 2. (A) Liver (×40, hematoxylin and eosin [H&E] stain): Largely preserved hepatic architecture with focal hepatocyte ballooning and marked and diffuse bile duct injury. (B) Liver (×200, H&E): Marked bile duct injury with mild to focally moderate inflammatory infiltrate consisting of lymphocytes and rare plasma cells. Hepatocyte ballooning (arrow). (C) Liver (×400, H&E): Mild cholestasis (arrow, circle). (D) Kidney (×400, H&E): Interstitial inflammatory infiltrate, including eosinophils (arrow), are present within a background of tubular atrophy (star). Extravasated red blood cells are seen on the right.CC BY-NC-ND · PubMed Central

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Citations

Cites

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Research works printed but not linked: 14

  1. Warren, 2018, Semaglutide as a therapeutic option for elderly patients with type 2 diabetes: Pooled analysis of the SUSTAIN 1-5 trials, Diabetes Obes Metab., 20, 2291, 10.1111/dom.13331 · DOI
  2. Dhillon, 2018, Semaglutide: First global approval, Drugs., 78, 275, 10.1007/s40265-018-0871-0 · DOI · Paper page
  3. Powell, 2020, Oral semaglutide: The first-available noninjectable glucagon-like peptide 1 receptor agonist, Clin Ther., 42, 2100, 10.1016/j.clinthera.2020.07.017 · DOI
  4. 2019, Oral semaglutide (Rybelsus) for type 2 diabetes, Med Lett Drugs Ther, 61, 166
  5. Yin, 2021, Comprehensive analysis of the safety of semaglutide in type 2 diabetes: A meta-analysis of the SUSTAIN and PIONEER trials, Endocr J., 68, 739, 10.1507/endocrj.EJ21-0129 · DOI
  6. Leehey, 2021, Acute kidney injury associated with semaglutide, Kidney Med., 3, 282, 10.1016/j.xkme.2020.10.008 · DOI
  7. Chalasani, 2015, Features and outcomes of 899 patients with drug-induced liver injury: The DILIN prospective study, Gastroenterology., 148, 1340, 10.1053/j.gastro.2015.03.006 · DOI · Paper page
  8. Chalasani, 2008, Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States, Gastroenterology., 135, 1924, 10.1053/j.gastro.2008.09.011 · DOI · Paper page
  9. Fontana, 2009, Drug-induced liver injury Network (DILIN) prospective study: Rationale, design and conduct, Drug Saf., 32, 55, 10.2165/00002018-200932010-00005 · DOI · Paper page
  10. Twarog, 2019, Intestinal permeation enhancers for oral delivery of macromolecules: A comparison between salcaprozate sodium (SNAC) and sodium caprate (C10), Pharmaceutics., 11, 78, 10.3390/pharmaceutics11020078 · DOI
  11. Ieiri, 2009, Genetic polymorphisms of uptake (OATP1B1, 1B3) and efflux (MRP2, BCRP) transporters: Implications for inter-individual differences in the pharmacokinetics and pharmacodynamics of statins and other clinically relevant drugs, Expert Opin Drug Metab Toxicol., 5, 703, 10.1517/17425250902976854 · DOI
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  14. Fitzky, 1998, Mutations in the Δ7-sterol reductase gene in patients with the Smith–Lemli–Opitz syndrome, Proc Natl Acad Sci U S A., 95, 8181, 10.1073/pnas.95.14.8181 · DOI · Paper page

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Metadata

Authors
Ma, J., Mathur, K., Muldoon, J. L., Ghabril, M., Chalasani, N., & Vuppalanchi, R.
Affiliations
  • Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN
  • Department of Pathology, Indiana University School of Medicine, Indianapolis, IN
Venue
ACG Case Reports Journal
Published
2022-12
Volume
9
Issue
12
Pages
e00922
ISSN
2326-3253
Cited by
12
References
2
Language
en

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CoChat. (2026). Citation check: Progressive Cholestasis and Biliary Cirrhosis After Initiating Oral Semaglutide: Report From the Drug-Induced Liver Injury Network. https://app.cochat.ai/papers/10.14309/crj.0000000000000922
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Ma, J., Mathur, K., Muldoon, J. L., Ghabril, M., Chalasani, N., & Vuppalanchi, R. (2022). Progressive Cholestasis and Biliary Cirrhosis After Initiating Oral Semaglutide: Report From the Drug-Induced Liver Injury Network. ACG Case Reports Journal. https://doi.org/10.14309/crj.0000000000000922

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