Vol. 5 No. 2 (2026): March-April
74-82
2026-04-30
Open Access

Parity-Dependent Pancreatic Morphological and Morphometric Changes in Intrahepatic Cholestasis of Pregnancy: An Autopsy Study

Bobur Khoshimov
Sherzod Kenjayev
https://doi.org/10.56121/MSU-2026-2-00012

Received: 2026-02-27

Published: 2026-04-30

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Abstract

Aim. To characterise the morphological and morphometric changes of the pancreas, and their relationship with hepatic injury and pregnancy parity, in women who died with intrahepatic cholestasis of pregnancy (ICP).
Materials and Methods. An autopsy-based morphological and quantitative morphometric study was performed on liver and pancreatic tissue from 51 women who died with severe ICP (Republican Scientific and Practical Center of Pathological Anatomy, 2013–2023), compared with 12 fertile-age controls who died of acute myocardial infarction. Sections were stained with haematoxylin–eosin and digitised for morphometry (12 parameters) in 28 index cases and controls; means were compared using Student’s t-test.
Results. ICP livers showed centrilobular and midzonal hepatocellular cholestasis, bile-pigment accumulation, hydropic dystrophy and necrobiosis (54.2%), with canalicular bile stasis in 75% of cases. The pancreas showed bile reflux into major and lobular ducts, segmental acinar necrosis, vacuolar dystrophy, interstitial oedema, periductal infiltration and progressive fibrosis. All 12 morphometric indices differed significantly from controls (P<0.01–P<0.001), and severity increased with parity, being most pronounced in the third and fourth pregnancies.
Conclusion. ICP is a systemic, bile-acid-mediated toxic condition producing quantifiable, parity-dependent pancreatic injury alongside hepatic cholestasis, supporting closer pancreatic surveillance in severe or recurrent ICP.


 

Keywords

List of references

  1. Gandhi S, Barsanti-Innes B, Jolicoeur G, Nwokoro IN. Intrahepatic cholestasis of pregnancy. Clin Liver Dis. 2026;30(3):677–699. https://doi.org/10.1016/j.cld.2026.04.009.

  2. Jurk S, Kremer A, Schleussner E. The latest on intrahepatic cholestasis of pregnancy – update 2026. Geburtshilfe Frauenheilkd. 2026;86(6):528–537. https://doi.org/10.1055/a-2845-6610.

  3. Capatina N, Ovadia C. Meta-analyses in cholestatic pregnancy: the outstanding clinical questions. Obstet Med. 2024;17(3):147–151. https://doi.org/10.1177/1753495X241251425.

  4. Niculae LE, Petca A. Intrahepatic cholestasis of pregnancy: neonatal impact through the lens of current evidence. Biomedicines. 2025;13(9):2066. https://doi.org/10.3390/biomedicines13092066.

  5. Kothari S, Afshar Y, Friedman LS, Ahn J. AGA clinical practice update on pregnancy-related gastroin-testinal and liver disease: expert review. Gastroenterology. 2024;167(5):1033–1045. https://doi.org/10.1053/j.gastro.2024.06.014.

  6. Zollner G, Trauner M. Mechanisms of cholestasis. Clin Liver Dis. 2008;12(1):1–26.

  7. Yuan S, Zhou S. Mechanistic basis and translational potential of traditional Chinese medicine in the treatment of cholestasis: a narrative review. Hepat Med. 2026;18:609530. https://doi.org/10.2147/HMER.S609530.

  8. Tang D, Yang J, Shi X, Gu X, Zhao L. Activation of the TGR5/cAMP/PKA/CREB axis in cholangiocytes mediates epithelial-mesenchymal transition and fibrosis in hepatolithiasis. Biol Direct. 2026;21(1). https://doi.org/10.1186/s13062-026-00783-7.

  9. Huang X, Liao E, Chen A, Shao Y. Mechanism of mitochondrial dysfunction on placental trophoblastic cells in intrahepatic cholestasis of pregnancy. J Mol Histol. 2025;56(3):140. https://doi.org/10.1007/s107 35-025-10427-1.

  10. Xu ZT, Ge LX, Luo L, Ma HY, Xiao H, Ding YB. PIP2 accumulation in the spongiotrophoblast drives trophoblast apoptosis in intrahepatic cholestasis of pregnancy. Mol Reprod Dev. 2026;93(4):e70105. https://doi.org/10.1002/mrd.70105.

  11. Tyrmi JS, Karjalainen J, Venkatesh SS, Benoit-Pilven C, Lemmelä SM, Brunak S, et al. Genome-wide meta-analysis identifies genetic drivers of bile acid metabolism in intrahepatic cholestasis of pregnancy. Nat Commun. 2026;17(1). https://doi.org/10.1038/s41467-026-73122-z.

  12. English N, Rao J. Acute fatty liver of pregnancy with hypoglycaemia, diabetes insipidus and pancreatitis, preceded by intrahepatic cholestasis of pregnancy. BMJ Case Rep. 2015;2015:bcr2015209649. https://doi.org/10.1136/bcr-2015-209649.

  13. Yosief S, Chen W, Wescoe K, Branch MS, Bashir M, Wegermann K. Perplexing severe cholestasis in the postpartum period. ACG Case Rep J. 2026;13(5):e02115. https://doi.org/10.14309/crj.00000000000021 15.

  14. Beuers U. Drug insight: mechanisms and sites of action of ursodeoxycholic acid in cholestasis. Nat Clin Pract Gastroenterol Hepatol. 2006;3(6):318–328.

  15. Chen Y, Zhang H, Ning W, Chen Y, Wen C. The impact of intrahepatic cholestasis on pregnancy outcomes: a retrospective cohort study. BMC Gastroenterol. 2023;23(1):16. https://doi.org/10.1186/s12876-023-02652-3.

  16. Keles E, Kaya L, Ogunc YT, Kaya Z, Baydili KN, Kumru P. Impact of maternal nutrition and gesta¬tional weight gain on perinatal outcomes in intrahepatic cholestasis of pregnancy. Rev Assoc Med Bras. 2026;72(3):e20251795. https://doi.org/10.1590/1806-9282.20251795.

  17. Öztürk Ö, Çirkin Tekeş G, Şimşek M, Küçükkayıkçı AS, Yakut Yücel K. The evaluation of Xenin-25 levels in intrahepatic cholestasis of pregnancy and comparison with healthy pregnant women. BMC Pregnancy Childbirth. 2026;26(1). https://doi.org/10.1186/s12884-026-09234-7.

  18. Tsuru T, Watanabe T, Kouzu K, Yamagishi Y, Einama T, Yamasaki T, et al. A simple morphometric algorithm based on nuclear atypia features of invasive breast carcinoma: relationship with nuclear grade, Ki-67 level, and hormone receptor status. Breast Cancer. 2026;33(4):905–918. https://doi.org/10.1007/s1 2282-026-01870-3.

  19. Ono D, Kawai H, Kuwahara H, Yokota T. Refining muscle morphometry through machine learning and spatial analysis. Neuropathol Appl Neurobiol. 2025;51(2):e70012. https://doi.org/10.1111/nan.70012.

  20. Sales DC, Fontes CC, Zanella AP, Martinez C, Souza-Sporkens JC, Vanzela EC, et al. Maternal high-fat diet impairs pancreatic β-cell development and reduces VAMP-2 levels in islets of mouse offspring. J Dev Orig Health Dis. 2026;17:e32. https://doi.org/10.1017/S2040174426100646.

  21. Kumar PU, Ramalaxmi BA, Venkiah K, Sesikeran B. Effect of maternal undernutrition on human foetal pancreas morphology in second trimester of pregnancy. Indian J Med Res. 2013;137(2):302–307.

  22. Kodger J, Nadim H, Choucair I, Sutphin A, Eid T, El-Khoury JM. Rapid diagnosis of intrahepatic cholestasis of pregnancy (ICP): validation of an automated enzymatic total bile acid assay and assessment of ursodeoxycholic acid impact on bile acid profiles in an ICP cohort. J Appl Lab Med. 2026. https://doi.org/10.1093/jalm/jfag099.

About the Authors

Bobur Khoshimov
talaba00719941995@gmail.com
Alfraganus University
Sherzod Kenjayev
usmleu6@gmail.com
Fergana Medical Institute of Public Health

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1.
Parity-Dependent Pancreatic Morphological and Morphometric Changes in Intrahepatic Cholestasis of Pregnancy: An Autopsy Study. MSU [Internet]. 2026 Apr. 30 [cited 2026 Aug. 23];5(2):74-82. Available from: https://fdoctors.uz/index.php/journal/article/view/280
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