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Case Reports
. 2022 Dec 26;9(12):e00922.
doi: 10.14309/crj.0000000000000922. eCollection 2022 Dec.

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

Jiayi Ma  1 , Karan Mathur  1 , Jessica L Muldoon  2 , Marwan Ghabril  1 , Naga Chalasani  1 , Raj Vuppalanchi  1
Affiliations
Case Reports

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

Jiayi Ma et al. ACG Case Rep J. .

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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Figures

Figure 1.
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 2.
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.
See this image and copyright information in PMC

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