学术急诊医学档案

卷 14 编号 1 (2026)

Independent Predictors of Major Adverse Cardiac and Hepatic Outcomes Following Acute Liver Complications of Pregnancy; A Retrospective Cohort Study

学术急诊医学档案, 卷 14 编号 1 (2026), 1 七月 2025 , 第 e42 页
https://doi.org/10.22037/aaem.v14i1.3099

摘要

Introduction: Acute liver complications of pregnancy (ALCP) remain major contributors to maternal morbidity. This study aimed to characterize cardio-hepatic crosstalk and identify independent predictors of hepatic failure and major cardiovascular events in patients with ALCP.

Methods: This retrospective cohort study was conducted to investigate cardio-hepatic crosstalk, endothelial dysfunction, and cardiovascular risk stratification among pregnant women with ALCP (4 diagnostic categories: HELLP syndrome, pre-eclampsia with hepatic involvement, acute fatty liver of pregnancy, and intrahepatic cholestasis of pregnancy). Independent predictors of cardiac and hepatic outcomes following ALCP, among endothelial, cardiac, inflammatory, coagulation, and renal biomarkers, were detected using correlation, multivariable regression, and receiver operating characteristic (ROC) analyses.

Results: 400 patients with ALCP were studied. All 22 studied biomarkers differed significantly across diagnostic categories. The ratio of soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF ratio) correlated most strongly with N-terminal pro-B-type natriuretic peptide (NT-proBNP) (r = 0.57, p < 0.001) and independently predicted major cardiovascular events (adjusted odds ratio (OR) = 1.38, 95% confidence interval (CI) = 1.03–1.85). C-reactive protein and creatinine independently predicted hepatic failure, with C-reactive protein showing the highest discriminative accuracy (area under the ROC curve of 0.79 (95% CI: 0.69–0.89).

Conclusions: Hepatic and cardiovascular derangement in ALCP constitute an interconnected, biomarker-detectable syndrome, supporting integrated biomarker-guided risk stratification for emergency management and delivery-timing decisions.

关键词:
  • Biomarkers
  • Cardiovascular Risk Assessment
  • Endothelial Dysfunction
  • HELLP Syndrome
  • Liver Diseases
  • Pregnancy-Related
  • Pre-Eclampsia

参考

1. Alexander V, Benjamin SJ, Subramani K, Sathyendra S, Goel A. Acute liver failure in pregnancy. Indian J Gastroenterol. 2024;43(2):325-37.

2. Nelson DB, Byrne JJ, Cunningham FG. Acute Fatty Liver of Pregnancy. Clin Obstet Gynecol. 2020;63(1):152-64.

3. Byrne JJ, Seasely A, Nelson DB, McIntire DD, Cunningham FG. Comparing acute fatty liver of pregnancy from hemolysis, elevated liver enzymes, and low platelets syndrome. J Matern Fetal Neonatal Med. 2022;35(7):1352-62.

4. Dellavolpe J AKA. Liver Failure in the Critical Care Setting 2022 [Available from: https://deckerip.com/products/gastroenterology-hepatology-and-endoscopy/table-of-contents/?chapter_id=2006.

5. Walabh P, Karvellas CJ. What's new in the critical care management of acute liver failure: a focus on global accessibility. Expert Rev Gastroenterol Hepatol. 2025;19(10):1101-8.

6. Khatun A, Karim AMMN, Biswas AH, Parvez MTM. Pregnancy Outcome in Impaired Liver Function in Pre-eclampsia. Bangladesh Med J. 2020;49(2):9-13.

7. Rath W, Tsikouras P, Stelzl P. HELLP Syndrome or Acute Fatty Liver of Pregnancy: A Differential Diagnostic Challenge: Common Features and Differences. Geburtshilfe Frauenheilkd. 2020;80(5):499-507.

8. Morrison MA, Chung Y, Heneghan MA. Managing hepatic complications of pregnancy: practical strategies for clinicians. BMJ Open Gastroenterol. 2022;9(1):e000624.

9. Zhestkova NV, Ailamazyan EK, Kuzminykh TU, Marchenko NV. Characteristics of liver function in patients with preeclampsia. J Obstet Women's Dis. 2023;72(4):59-69.

10. Oliveira JC, Codes L, Lucca M, Soares MAP, Lyrio L, Bittencourt PL. Frequency and Severity of Liver Involvement in Hypertensive Disorders of Pregnancy. Arq Gastroenterol. 2022;59(3):340-4.

11. Hartley J, Marschall HU. The Effects of Liver Disease in Pregnancy on Mother and Child. In: Diseases of the Liver and Biliary System in Children2017. p. 81-96.

12. Zakrzewska A, Grzybowska ME, Wydra DG, Mazur-Ejankowska NK, Adrych K, Tylicki L, et al. Plasmapheresis for Suspected Drug-Induced Liver Injury During Pregnancy: A Multidisciplinary Diagnostic and Therapeutic Challenge. J Clin Med. 2025;14(23):8385.

13. Zhang J, Li Z, Feng L, Zhang J, Bai T, Jiang W. Hemodynamic impact of acute liver injury on cardiac function: An in silico study via a closed-loop cardiovascular model. PLoS Comput Biol. 2026;22(2):e1014006.

14. Tanaka A, Node K. Crosstalk between the liver and heart: revisited for prevention and treatment. ESC Heart Fail. 2020;7(6):4489-90.

15. Brankovic M, Lee P, Pyrsopoulos N, Klapholz M. Cardiac Syndromes in Liver Disease: A Clinical Conundrum. J Clin Transl Hepatol. 2023;11(4):975-86.

16. Lee MS, Eum KD, Christiani DC. Maternal Circulating sFlt-1:PlGF Ratio and Stillbirth. JAMA Netw Open. 2026;9(4):e267652.

17. Belovan BA, Raţiu AC, Sas I, Stana LG. Dynamic TyG-inflammation-endothelial trajectories and placental histopathology synergistically define a maternal-fetal vascular risk phenotype. Rom J Morphol Embryol. 2025;66(2):361-6.

18. Liu X, Si Y, Wang G, Meng Y, Li Q, Yang W. Placental IL-1β impairs endothelial functions by reducing VE-cadherin expression in PE. FASEB J. 2022;36(S1).

19. Kelly C, Pericleous M. Pregnancy-associated liver disease: a curriculum-based review. Frontline Gastroenterol. 2018;9(3):170-4.

20. Abbasi A. Management of Liver Diseases in Pregnancy. J Soc Obstet Gynaecol Pak. 2025;15(Supplement III):1-12.

21. Birkness-Gartman JE, Oshima K. Liver pathology in pregnancy. Pathol Int. 2022;72(1):1-13.

22. Hamidi F, Furtado RHM, Fagundes A, Jr., Zelniker TA. Editorial: Exploring modern approaches to address critical care challenges in risk stratification for cardiology. Front Cardiovasc Med. 2023;10:1326645.

23. Ertuğrul Ş, Golcuk Y. The Prognostic Value of MELD-XI Score in Emergency Department Patients with ST Segment Elevation Myocardial Infarction. Anatolian J Emerg Med. 2025;8(2):59-65.

24. Hodgson NR, Lindor RA, Monas J, Heller K, Kishi P, Thomas A, et al. Pregnancy-Related Heart Disease in the Emergency Department. J Pers Med. 2025;15(4):148.

25. Correale M, Tricarico L, Leopizzi A, Mallardi A, Mazzeo P, Tucci S, et al. Liver disease and heart failure. Panminerva Med. 2020;62(1):26-37.

26. Pillai KR, Selvarajan Chettiar K, Suresh M. Assessment of Cardiac Dysfunctions in Patients with Liver Cirrhosis Admitted in a Tertiary Care Centre. J Evol Med Dent Sci. 2023;12(11):331-5.

27. Sapmaz MA, Erbey S, Polat M, Kurt A, Kurt DS, Yücel KY, et al. The impact of biochemical marker levels in pregnant patients diagnosed with HELLP syndrome on predicting the progression and recovery timelines. EurRJ. 2025;11(5):868-77.

28. Maalbi O, Elachhab N, Elkabbaj A, Arfaoui M, Hindi S, Lahbabi S, et al. Management of Acute Fatty Liver of Pregnancy: A Retrospective Study of 12 Cases Compared With Data in the Literature. Cureus. 2025;17(6):e85753.

29. Kluivers ACM, Biesbroek A, Visser W, Saleh L, Russcher H, Danser AHJ, et al. Angiogenic imbalance in pre-eclampsia and fetal growth restriction: enhanced soluble fms-like tyrosine kinase-1 binding or diminished production of placental growth factor? Ultrasound Obstet Gynecol. 2023;61(4):466-73.

30. von See J, Limperger V, Pecks U, Eckmann-Scholz C. [Influences on Placental Growth Factor (PlGF) and Soluble fms-like Tyrosine Kinase-1 (sFlt-1) Concentration Levels at the Time of First Trimester Screening]. Z Geburtshilfe Neonatol. 2016;220(4):166-72. German.

31. Hastie R, Bergman L, Walker SP, Kaitu'u-Lino T, Hannan NJ, Brownfoot F, et al. Associations Between Soluble fms-Like Tyrosine Kinase-1 and Placental Growth Factor and Disease Severity Among Women With Preterm Eclampsia and Preeclampsia. J Am Heart Assoc. 2022;11(16):e024395.

32. Ren Z, Cui N, Zhu M, Khalil RA. Placental growth factor reverses decreased vascular and uteroplacental MMP-2 and MMP-9 and increased MMP-1 and MMP-7 and collagen types I and IV in hypertensive pregnancy. Am J Physiol Heart Circ Physiol. 2018;315(1):H33-h47.

33. Chapman H, Eddy AC, Bidwell GL, George EM. Abstract P308: Differential VEGF-Dependent Induction of sFlt-1 From Vascular Endothelial and Placental Cells. Hypertension. 2018;72(Suppl_1):AP308-AP.

34. Ardani AA, Fitriati M, Airlangga PS, Harjana LT, Wardhana MP. Soluble FMS-like tyrosine kinase-1/Pro-angiogenic placental growth factor (sFlt-1/PlGF) ratio as an early predictor for oxygenation impairment in preeclampsia. Int J Innov Res Sci Stud. 2025;8(4):1370-5.

35. Gurnadi JI, Mose J, Handono B, Satari MH, Anwar AD, Fauziah PN, et al. Difference of concentration of placental soluble fms-like tyrosine kinase-1(sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio in severe preeclampsia and normal pregnancy. BMC Res Notes. 2015;8:534.

36. Altendahl M, Mok T, Adimkpayah E, Goldstein J, Lin J, Afshar Y. Vascular malperfusion and abruption are prevalent in placentas from pregnancies with congenital heart disease and not associated with cardiovascular risk. Sci Rep. 2023;13(1):1439.

37. Benagiano M, Mancuso S, Brosens JJ, Benagiano G. Long-Term Consequences of Placental Vascular Pathology on the Maternal and Offspring Cardiovascular Systems. Biomolecules. 2021;11(11):1625.

38. Neuman RI, Hesselink ERM, Saleh L, van den Meiracker AH, Danser AHJ, Visser W. Angiogenic markers are elevated in women with acute fatty liver of pregnancy. Ultrasound Obstet Gynecol. 2020;56(3):465-6.

39. Mezaal FN, Mishlish SM, Dawood KF. Prospective randomized controlled trial of liver function tests in unstable angina risk prediction. JUAPS. 2024;18(2):154.

40. Noda T, Kamiya K, Hamazaki N, Nozaki K, Ichikawa T, Yamashita M, et al. Associations of severity of liver damages with physical function and prognosis in patients with heart failure. Eur J Prev Cardiol. 2021;28(Supplement_1):zwab061. 34.

41. Klisić A, Kavarić N, Ninić A. Are liver function biomarkers independently associated with Framingham risk score in women? Srp Arh Celok Lek. 2020;148(7-8):423-9.

42. Zhou Q, Pei S, Yang S, Liu T, Wu J, Xu Z, et al. A comprehensive review of C-reactive protein testing methods: from current status to future prospects. Analyst. 2026;151(3):718-40.

43. Shishehbor MH, Bhatt DL, Topol EJ. Using C-reactive protein to assess cardiovascular disease risk. Cleve Clin J Med. 2003;70(7):634-40.

44. Ullah A, Sajid S, Qureshi M, Kamran M, Anwaar MA, Naseem MA, et al. Novel Biomarkers and the Multiple-Marker Approach in Early Detection, Prognosis, and Risk Stratification of Cardiac Diseases: A Narrative Review. Cureus. 2023;15(7):e42081.

45. Parikh NI, Laria B, Nah G, Singhal M, Vittinghoff E, Vieten C, et al. Cardiovascular Disease-Related Pregnancy Complications Are Associated with Increased Maternal Levels and Trajectories of Cardiovascular Disease Biomarkers During and After Pregnancy. J Womens Health (Larchmt). 2020;29(10):1283-91.

46. Lewey J. Challenges and opportunities to improving research in maternal cardiovascular health. Nat Cardiovasc Res. 2023;2(1):6-7.

47. Xiao L, Zeng L, Wang J, Hong C, Zhang Z, Wu C, et al. Development and Validation of Machine Learning-Based Marker for Early Detection and Prognosis Stratification of Nonalcoholic Fatty Liver Disease. Adv Sci (Weinh). 2025;12(33):e10527.

48. Adams AD, Benner RS, Riggs TW, Chescheir NC. Use of the STROBE Checklist to Evaluate the Reporting Quality of Observational Research in Obstetrics. Obstet Gynecol. 2018;132(2):507-12.

49. Gong T, Brew B, Sjölander A, Almqvist C. Towards non-conventional methods of designing register-based epidemiological studies: An application to pediatric research. Scand J Public Health. 2017;45(17_suppl):30-5.

50. Malhamé I, Danilack VA, Raker CA, Hardy EJ, Spalding H, Bouvier BA, et al. Cardiovascular severe maternal morbidity in pregnant and postpartum women: development and internal validation of risk prediction models. Obstet Anesth Dig. 2022;42(1):26.

51. de Sausmarez E, Crowest P, Fry S, Hodgson L. Predicting outcome in liver patients admitted to intensive care: A dual-centre non-specialist hospital external validation of the Liver injury and Failure evaluation score. J Intensive Care Soc. 2021;22(2):152-8.

52. Zahari Sham SY, Hanif E, Thambiah SC, Samsudin IN, Mohd Noor S, Osman M, et al. High sensitivity C-reactive protein (hsCRP): Its relationship with metabolic syndrome and Framingham Risk Score. Malays J Pathol. 2021;43(1):33-40.

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