GEBELİK İNTRAHEPATİK KOLESTAZINDA KARACİĞER FONKSİYON ENDEKSLERİNİN DEĞERLENDİRİLMESİ: TANI YARARLIĞI VE YENİDOĞAN SONUÇLARI

Öz

Amaç: Gebelikte intrahepatik kolestaz (ICP), gebeliklerin %0,2-2'sinde görülen bir karaciğer hastalığıdır. Yoğun kaşıntı ve kan dolaşımında safra asitlerinin artmasıyla karakterizedir. Olumsuz neonatal sonuçların kesin olarak tanımlanması ve öngörülmesi çok önemlidir. Bu çalışma, ICP hastalarında karaciğerle ilgili APRI (aspartat aminotransferaz-trombosit), ALBI (albümin-bilirubin), PALBI (trombosit-albümin-bilirubin) ve FAR (fibrinojen/albümin oranı) değerinin tanısal performansını değerlendirmekte ve bunların gebelik sonuçlarıyla olan ilişkisini incelemektedir. Gereç ve Yöntem: Bu çalışma Ocak 2023-Ocak 2024 tarihleri arasında Ankara Etlik Şehir Hastanesi'nde tedavi gören 180 hastanın retrospektif analizidir. 90 ICP hastası (Grup 1) ile 90 kontrol hastası (Grup 2) karşılaştırıldı. PALBI, ALBI, APRI skorları ve FAR üçüncü trimester laboratuvar değerleri kullanılarak hesaplandı. Doğum ağırlığı, APGAR skorları, yenidoğan yoğun bakım ünitesine kabul, sepsis, solunum sıkıntısı ve neonatal ölümü içeren neonatal sonuçlar kaydedildi. İstatistiksel analiz, ROC (Receiver Operating Characteristics) eğrisi analizi ve Spearman korelasyonu ile yapıldı. Bulgular: ICP hastalarında PALBI, ALBI, APRI skorları ve FAR anlamlı olarak yüksekti (p<0,001). APRI puanı en yüksek tanısal performansı gösterdi (AUC: 0.870). PALBI skoru için cut-off değeri>-2,58 (sensivite %62, spesifite %81), ALBI skoru için >-2,47 (sensitive %67, spesifite %81), APRI skoru için >0,3 (sensivite %78, spesifite %68) idi. Yenidoğan sonuçları gruplar arasında anlamlı farklılık göstermedi. Yenidoğanlarda açlık safra asidi düzeyleri ve karaciğer hasarı belirteçleri ile olumsuz sonuçlar arasında bir korelasyon yoktu. Sonuç: Açlık safra asidi düzeylerinin test edilmesinin mümkün olmadığı merkezlerde PALBI, ALBI, APRI skorları ve FAR değeri intrahepatik gebelik kolestazı olan bireylerin değerlendirilmesinde alternatif bir yaklaşım sunmaktadır. Bu parametrelerin güvenilirliğini arttırmak için daha geniş hasta gruplarıyla gelecek çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

• Gebelikte intrahepatik kolestaz
• PALBI skoru
• açlık safra asitleri

EVALUATION OF LIVER FUNCTION INDICES IN INTRAHEPATIC CHOLESTASIS OF PREGNANCY: DIAGNOSTIC UTILITY AND NEONATAL OUTCOMES

Öz

Aim: Intrahepatic cholestasis of pregnancy (ICP) is a hepatic condition that occurs in 0.2-2% of pregnancies. It is characterized by intense itching and increased levels of bile acids in the bloodstream. Precise identification and anticipation of adverse neonatal outcomes are crucial. This study evaluates the diagnostic performance of liver-related scores—APRI (aspartate aminotransferase- platelet), ALBI (albumin-bilirubin), PALBI (platelet- albumin-bilirubin), and FAR (fibrinogen/albumin ratio) —in ICP patients and examines their relationship to pregnancy outcomes. Material and Method: This study was a retrospective analysis of 180 patients who were treated at Ankara Etlik City Hospital between January 2023 and January 2024. 90 ICP patients (Group 1) and 90 control patients (Group 2) were compared. The PALBI, ALBI, APRI scores, and FAR were calculated using third-trimester laboratory values. Neonatal outcomes, including birth weight, APGAR scores, NICU (neonatal intensive care unit) admission, sepsis, RDS (respiratory distress syndrome), and neonatal death were recorded. Statistical analyses included ROC (Receiver Operating Characteristics) curve analysis and Spearman correlation. Results: The PALBI, ALBI, APRI scores, and FAR were significantly higher in ICP patients (p<0.001). The APRI score showed the highest diagnostic performance (area under curve 0.870). Cut-off values were >-2.58 for PALBI (sensitivity 62%, specificity 81%), >-2.47 for ALBI (sensitivity 67%, specificity 81%), and >0.3 for APRI (sensitivity 78%, specificity 68%). Neonatal outcomes did not differ significantly between the groups. There was no correlation between fasting bile acid levels and liver damage markers with negative outcomes in newborns. Conclusion: In facilities where it is not possible to test fasting bile acid levels, PALBI, ALBI, APRI scores and FAR value offer an alternative approach to the evaluation of individuals with intrahepatic cholestasis of pregnancy (ICP). Future studies with larger patient groups are needed to increase the reliability of these parameters.

Anahtar Kelimeler

• Intrahepatic cholestasis of pregnancy
• PALBI score
• fasting bile acids

Kaynakça

1. 1.Sahni A, Jogdand SD. Effects of intrahepatic cholestasis on the foetus during pregnancy. Cureus. 2022;14(10):e30657. doi:10.7759/ cureus.30657
2. 2.Williamson C, Geenes V. Intrahepatic Cholestasis of Pregnancy. Obstet Gynecol. 2014;124(1):120. doi:10.1097/ AOG.0000000000000346
3. 3.Di Mascio D, Quist-Nelson J, Riegel M, et al. Perinatal death by bile acid levels in intrahepatic cholestasis of pregnancy: a systematic review. J Matern Fetal Neonatal Med. 2021;34(21):3614-3622. doi:10. 1080/14767058.2019.1685965
4. 4.Hobson S, Gandhi S, Sobel M. Intrahepatic cholestasis of pregnancy. CMAJ Can Med Assoc J/J Assoc Medicale Can. 2022;194(48):E1650. doi:10.1503/cmaj.220334
5. 5.Omeroglu I, Golbasi H, Bayraktar B, et al. Modified myocardial performance index for evaluation of fetal heart function and perinatal outcomes in intrahepatic pregnancy cholestasis. Int J Cardiovasc Imaging. 2023;39(5):907-914. doi:10.1007/s10554-022-02789-4
6. 6.Diken Z, Usta IM, Nassar AH. A clinical approach to intrahepatic cholestasis of pregnancy. Am J Perinatol. 2014;31(1):1-8. doi:10.1055/s-0033-1333673
7. 7.Walker IA, Nelson-Piercy C, Williamson C. Role of bile acid measurement in pregnancy. Ann Clin Biochem. 2002;39(Pt 2):105-113. doi:10.1258/0004563021901856
8. 8.Cui Y, Xu B, Zhang X, He Y, Shao Y, Ding M. Diagnostic and therapeutic profiles of serum bile acids in women with intrahepatic cholestasis of pregnancy-a pseudo-targeted metabolomics study. Clin Chim Acta. 2018;483:135-141. doi:10.1016/j.cca.2018.04.035

9. 9.Johnson PJ, Berhane S, Kagebayashi C, et al. Assessment of liver function in patients with hepatocellular carcinoma: A new evidence-based approach—The ALBI Grade. J Clin Oncol. 2015;33(6):550-558. doi:10.1200/JCO.2014.57.9151
10. 10.Lin ZH, Xin YN, Dong QJ, et al. Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatol Baltim Md. 2011;53(3):726-736. doi:10.1002/hep.24105
11. 11.Wong WG, Perez Holguin RA, Tarren AY, et al. Albumin-bilirubin score is superior to platelet-albumin-bilirubin score and model for end-state liver disease sodium for predicting posthepatectomy liver failure. J Surg Oncol. 2022;126(4):667-679. doi:10.1002/jso.26981
12. 12.Usta CS, Atik TK, Ozcaglayan R, Bulbul CB, Camili FE, Adali E. Does the fibrinogen/albumin ratio predict the prognosis of pregnancies with abortus imminens? Saudi Med J. 2021;42(3):255-263. doi:10.15537/smj.2021.42.3.20200695
13. 13.Masson E. Society for Maternal-Fetal Medicine Consult Series #53: Intrahepatic cholestasis of pregnancy: Replaces Consult #13, April 2011. EM-Consulte. Accessed May 29, 2024. https://www. em-consulte.com/article/1422666/society-for-maternal-fetal-medicine- consult-series
14. 14.Hansmann J, Evers MJ, Bui JT, et al. Albumin-Bilirubin and Platelet- Albumin-Bilirubin Grades accurately predict overall survival in high-risk patients undergoing conventional transarterial chemoembolization for hepatocellular carcinoma. J Vasc Interv Radiol. 2017;28(9):1224-1231.e2. doi:10.1016/j.jvir.2017.05.020
15. 15.Jayachandran AK, Nelson V, Anisha K. APRI as a predictor of severe dengue fever. J Fam Med Prim Care. 2024;13(2):613-618. doi:10.4103/jfmpc.jfmpc_1127_23
16. 16.Geenes V, Lövgren-Sandblom A, Benthin L, et al. The reversed feto- maternal bile acid gradient in intrahepatic cholestasis of pregnancy is corrected by ursodeoxycholic acid. Plos One. 2014;9(1):e83828. 119 doi:10.1371/journal.pone.0083828
17. 17.Geenes V, Williamson C. Intrahepatic cholestasis of pregnancy. World J Gastroenterol. 2009;15(17):2049-2066. doi:10.3748/ wjg.15.2049
18. 18.Chen J, Li Q, Ma J. Maternal serum, placental, and umbilical venous blood irisin levels in intrahepatic cholestasis of pregnancy. J Matern-Fetal Neonatal Med. 2021;34(15):2403-2410. doi:10.1080/1 4767058.2019.1667322
19. 19.Agaoglu RT, Celik OY, Yakut K, Celen S, Caglar AT. Maternal serum calprotectin level in intrahepatic cholestasis of pregnancy. J Obstet Gynaecol Res. 2021;47(10):3456-3463. doi:10.1111/jog.14925
20. 20.Kirbas A, Biberoglu E, Ersoy AO, et al. The role of interleukin-17 in intrahepatic cholestasis of pregnancy. J Matern-Fetal Neonatal Med. 2016;29(6):977-981. doi:10.3109/14767058.2015.1028354
21. 21.Biberoglu E, Kirbas A, Daglar K, et al. Role of inflammation in intrahepatic cholestasis of pregnancy. J Obstet Gynaecol Res. 2016;42(3):252-257. doi:10.1111/jog.12902
22. 22.Aksan Desteli G, Sahin-Uysal N, Cok T, Gulumser C, Kalayci H, Yanik FF. First trimester maternal serum PAPP-A levels and associated pregnancy complications in intrahepatic cholestasis of pregnancy. Clin Exp Obstet Gynecol. 2016;43(5):673-677.
23. 23.Tolunay HE, Kahraman NÇ, Varlı EN, et al. First-trimester aspartate aminotransferase to platelet ratio index in predicting intrahepatic cholestasis in pregnancy and its relationship with bile acids: A pilot study. Eur J Obstet Gynecol Reprod Biol. 2021;256:114-117. doi:10.1016/j.ejogrb.2020.11.014
24. 24.Wai CT, Greenson JK, Fontana RJ, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatol Baltim Md. 2003;38(2):518-526. doi:10.1053/jhep.2003.50346
25. 25.Rungta S, Kumari S, Deep A, Verma K, Swaroop S. APRI and FIB- 4 performance to assess liver fibrosis against predefined Fibroscan values in chronic hepatitis C virus infection. J Fam Med Prim Care. 2021;10(11):4082-4088. doi:10.4103/jfmpc.jfmpc_666_21
26. 26.Obut M, Kından A, Ibanoğlu MC, et al. Liver damage parameters and peripheral blood parameters for prediction and diagnosis of intrahepatic cholestasis in pregnancy. J Obstet Gynaecol Res. 2024;50(2):196-204. doi:10.1111/jog.15837
27. 27.Xu SX, Yang F, Ge N, Guo JT, Sun SY. Role of albumin-bilirubin score in non-malignant liver disease. World J Gastroenterol. 2024;30(9):999-1004. doi:10.3748/wjg.v30.i9.999
28. 28.Liu PH, Hsu CY, Hsia CY, et al. ALBI and PALBI grade predict survival for HCC across treatment modalities and BCLC stages in the MELD Era. J Gastroenterol Hepatol. 2017;32(4):879-886. doi:10.1111/jgh.13608
29. 29.Lu LH, Zhang YF, Mu-Yan C, et al. Platelet-albumin-bilirubin grade: Risk stratification of liver failure, prognosis after resection for hepatocellular carcinoma. Dig Liver Dis 2019;51(10):1430-1437. doi:10.1016/j.dld.2019.04.006
30. 30.Sun D wei, An L, Lv G yue. Albumin-fibrinogen ratio and fibrinogen- prealbumin ratio as promising prognostic markers for cancers: an updated meta-analysis. World J Surg Oncol. 2020;18:9. doi:10.1186/s12957-020-1786-2
31. 31.Glantz A, Marschall HU, Mattsson LA. Intrahepatic cholestasis of pregnancy: Relationships between bile acid levels and fetal complication rates. Hepatol Baltim Md. 2004;40(2):467-474. doi:10.1002/ hep.20336
32. 32.Lee RH, Kwok KM, Ingles S, et al. Pregnancy outcomes during an era of aggressive management for intrahepatic cholestasis of pregnancy. Am J Perinatol. 2008;25(6):341-345. doi:10.1055/s-2008-1078756
33. 33.Ovadia C, Seed PT, Sklavounos A, et al. Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses. Lancet Lond Engl. 2019;393(10174):899-909. doi:10.1016/S0140-6736(18)31877-4