The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Progressive Cholestasis and Biliary Cirrhosis After Initiating Oral Semaglutide: Report From the Drug-Induced Liver Injury Network
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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![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.](/paper-figures/e3f374e3b225426f8ca3652a4f06a8db/progressive-cholestasis-and-biliary-cirrhosis-after-initiating-oral-semaglutide-figure-2.jpg)
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“Despite their widespread use by millions of patients, there have only been a handful of DILI cases attributed to glucagon-like peptide-1 (GLP-1) receptor agonists, although cholecystitis is more frequent compared with placebo-treated patients.66–68”
From The contemporary epidemiology, causes, and management of drug-induced liver injury (2026) · cites this paper as [67]
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Cites
Efficacy and safety of once-weekly semaglutide in adults with overweight or obesity: a meta-analysis
Zhong, P., Zeng, H., Huang, M., Fu, W., & Chen, Z. (2022) · Endocrine · doi:10.1007/s12020-021-02945-1 · Cited by 74
Yabe, D., Deenadayalan, S., Horio, H., Kaneto, H., Jensen, T. B., Terauchi, Y., Yamada, Y., & Inagaki, N. (2022) · Journal of Diabetes Investigation · doi:10.1111/jdi.13764 · Cited by 23
Research works printed but not linked: 14
- 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
- Dhillon, 2018, Semaglutide: First global approval, Drugs., 78, 275, 10.1007/s40265-018-0871-0 · DOI · Paper page
- 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
- 2019, Oral semaglutide (Rybelsus) for type 2 diabetes, Med Lett Drugs Ther, 61, 166
- 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
- Leehey, 2021, Acute kidney injury associated with semaglutide, Kidney Med., 3, 282, 10.1016/j.xkme.2020.10.008 · DOI
- 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
- 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
- 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
- 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
- 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
- Keppler, 2017, Progress in the molecular characterization of hepatobiliary transporters, Dig Dis., 35, 197, 10.1159/000450911 · DOI · Paper page
- Witsch-Baumgartner, 2001, Mutations in the human DHCR7 gene, Hum Mutat., 17, 172, 10.1002/humu.2 · DOI
- 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
Cited by
Semaglutide-Induced Liver Injury
Kalsi, H., Arora, S. S., Essilfie-Quaye, K., Bassi, R., Akhavan, N., Perbtani, Y., & Brar, T. S. (2025) · ACG Case Reports Journal · doi:10.14309/crj.0000000000001776 · Cited by 6
The contemporary epidemiology, causes, and management of drug-induced liver injury
Swanson, L., & Fontana, R. J. (2026) · Hepatology Communications · doi:10.1097/hc9.0000000000001011
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
- ORCID
- Ma, Jiayi
- Venue
- ACG Case Reports Journal
- Published
- 2022-12
- Volume
- 9
- Issue
- 12
- Pages
- e00922
- ISSN
- 2326-3253
- PMC
- PMC9794239
- Cited by
- 12
- References
- 2
- Language
- en
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