Homiladorlikdagi jigar ichi xolestazi

Ishorat qoʻshish
Vikipediya, ochiq ensiklopediya
Homiladorlik davridagi jigar ichi xolestazi
Cholestasis high mag
Jigar xolestazining mikroskopda ko'rinishi
Mutaxassislik Gepatologiya Ginekologiya
Sabablari Aniq emas
Tashxis usullari Qon biokimyoviy tahlili

Homiladorlikdagi intragepatik xolestaz, shuningdek, akusherlik xolestazi, homiladorlik xolestazi, homiladorlik sariqligi va prurigo gravidarum sifatida ham tanilgan homiladorlik davrida xolestaz yuzaga kelishi bilan kechadigan tibbiy holat[1]. Odatda qichishish bilan kechadi va ona va chaqaloq uchun asoratlarni keltirib chiqarishi mumkin[2].

Pruritus (qichishish) homiladorlikning keng tarqalgan alomati bo'lib, ayollarning taxminan 23 foizida uchraydi[3]. Ko'pincha qichishish terining o'zgarishi, ayniqsa qorin bo'shlig'ining o'zgarishi natijasida yuzaga keladigan kichik bezovtalik holatidir. Biroq, qichishish homiladorlik xolestazining alomati bo'lishi mumkin bo'lgan holatlar ham mavjud. Qichishish odatda qo'l kaftlarida va oyoq tagida sezilsa ham, tananing har qanday joyida paydo bo'lishi mumkin.

Homiladorlik xolestazi odatda homiladorlikning uchinchi trimestrida sodir bo'ladi, ammo homiladorlikning istalgan vaqtida boshlanishi ham mumkin.

Belgilari[tahrir | manbasini tahrirlash]

Ushbu kasallikka chalingan ayollarning aksariyati uchinchi trimestrda (shu bilan birga u yetti haftada paydo bo'lishi mumkin) toshmasiz qichishish bilan birga keladi. Odatda, qichishish qo'llarning kaftlari va oyoq tagida bo'ladi, lekin tananing boshqa sohalarida ham bo'lishi mumkin.

Homiladorlik xolestazining o'ziga xos belgilariga quyidagi alomatlar kiradi[4]:

Keng tarqalgan belgilari:

  • Qichishish, ayniqsa qo'l kaftlari va oyoq tagida toshmasiz qichishish
  • Kechqurun ko'proq seziladigan qichishish
  • Siydik rangining to'qroq bo'lishi

Kam tarqalgan belgilari:

  • Najas rangi ochiqroq bo'lishi
  • Qon ivish vaqtining ko'payishi (ehtimol , K vitamini yetishmasligi tufayli)
  • Charchoq
  • Ko'ngil aynishning ortishi
  • Ishtahaning pasayishi
  • Sariqlik (ayollarning 10% dan kamrog'ida)
  • Qorinning yuqori o'ng kvadrat sohasida og'riq

Homiladorlik xolestazi bilan og'riganlarning hammasida ham yuqoridagi belgilar uchramasligi mumkin.

Mexanizmi[tahrir | manbasini tahrirlash]

Homiladorlik intragepatik xolestazining sabablari hali ham to'liq aniqlanmagan, ammo genetik o'zgarishlar[5][6], gormonlar va atrof-muhitning kombinatsiyasi tufayli yuzaga keladi deb taxmin qilinadi[7]. Gormonlar, atrof-muhit va genetik omillar bu holatga hissa qo'shishi mumkin[8].

  • Homiladorlik xolestazi odatda uchinchi trimestrda gormonlar darajasi eng yuqori bo'lgan vaqtda sodir bo'ladi.
  • Yuqori gormonlar darajasi bilan bog'liq bo'lgan egizak va uchlik homiladorlik homiladorlik xolestazining yuqori chastotasini ko'rsatadi[9].
  • Homiladorlik xolestazi tug'ruqdan keyin, platsenta gormoni ishlab chiqarish to'xtatilganda tezda yo'qoladi.
  • Dastlabki sinflardagi yuqori dozali estrogeni bo'lgan og'iz kontraseptiv tabletkalari homiladorlik xolestaziga olib kelishi mumkin.

Estrogenlar[tahrir | manbasini tahrirlash]

Estrogenlar, xususan, estradiol-17β-D-glyukuronid kabi glyukuronidlar gepatotsitlar tomonidan o't kislotasi so'rilishini kamaytirish orqali hayvonlarda o'tkazilgan tadqiqotlarda xolestazni keltirib chiqarishi ko'rsatilgan[10].

Progesteron[tahrir | manbasini tahrirlash]

Homiladorlikning uchinchi trimestrida progesteron bilan davolash homiladorlik xolestazi rivojlanishi bilan bog'liqligi aniqlangan va progesteron metabolitlari darajasi, xususan, sulfatlangan progesteron [11] homiladorlik xolestazi bilan og'rigan bemorlarda bu bilan kasallanmagan ayollarga qaraganda yuqori, bu homiladorlik xolestazida progesteron estrogenga qaraganda muhimroq rol o'ynashi mumkinligini ko'rsatadi[12].

Genetik omillar[tahrir | manbasini tahrirlash]

Oilalarda homiladorlik xolestazi holatlarining klasterlanishi, uning tezligining geografik o'zgarishi va keyingi homiladorliklarning 45-70% da bu holatning takrorlanishi kasallikning genetik komponentini ko'rsatadi[8]. Homiladorlik xolestazi holatlarida fosfatidilxolinning safroga sekretsiyasini nazorat qiluvchi gepatotsellyulyar transport oqsili ABCB4 (MDR3) dagi genetik mutatsiyalar aniqlangan[13].

Jigar o't tuzlarini tashuvchi molekulalariga ta'sir qiluvchi genetik mutatsiyalar, shuningdek , progressiv oilaviy intragepatik xolestaz bo'lgan bemorlarda ham topilgan. Ushbu kasallik bilan og'rigan bemorlarning onalarida homiladorlik xolestazi bilan kasallanish ko'proq ekanligi aniqlandi, bu esa ushbu mutatsiyalarning geterozigota tashuvchilari ham bu kasallikka moyil ekanligini ko'rsatadi[8].

Safro tuzlarini tashuvchi transport molekulalarda genetik o'zgarishlarga qo'shimcha ravishda, yuqori darajadagi estrogen glyukuronidlari safro tuzi eksport pompasini (BSEP) ABCB11 ni ingibitsiya qilishi[14], va yuqori darajadagi progesteron ABCB4 (MDR3) fosfolipid tashuvchisi ishini susaytirishi aniqlangan[15].

Binobarin, gepatotsitlardagi safro sekretsiyasida ishtirok etuvchi oqsillarning irsiy mutatsiyalari ham homiladorlik davrida yuqori darajadagi gormon metabolitlari tomonidan ushbu oqsillar ishini susaytirishi orqali intragepatik xolestaz patogenezida rol o'ynashi mumkin[7].

Atrof-muhit omillari[tahrir | manbasini tahrirlash]

Homiladorlikdagi jigar ichi xolestazining bir qator xususiyatlari atrof-muhit omillari ham kasallikda rol o'ynashini ko'rsatadi:

  • Xabar qilinishicha, homiladorlik xolestazi bilan kasallanish yozga qaraganda qishda ko'proq bo'ladi[16].
  • Chilida bu kasallik bilan kasallanish 1975-yilgacha bo'lgan homiladorlikning 14 foizidan 2016-yilda 4 foizga kamaydi[17].
  • Homiladorlik xolestazi keyingi homiladorlikda 60% dan 90% gacha takrorlanadi.
  • Qon zardobidagi selenning past darajalari homiladorlik xolestazi bilan bog'langan[18], ammo selenning safro sekretsiyasidagi roli noma'lum.

Diagnostikasi[tahrir | manbasini tahrirlash]

Homiladorlik xolestazi qon analizlari, shu jumladan zardobdagi safro kislota testi va jigar funksiyasi testi bilan tashxislanadi. Ko'pgina homilador ayollar vaqti-vaqti bilan qichishishni boshdan kechirishsa-da, ko'rinadigan toshmalarsiz qichishish yoki doimiy yoki keng qamrovli qichishish belgilari haqida akusherga yoki ginekologga xabar berish kerak. Shuni ta'kidlash kerakki, qichishish darajasi o't kislotasi darajasiga bog'liq emas (homiladorlik xolestazida o'lik tug'ilishning eng ko'p sababi hisoblanadi), Homiladorlik xolestazidagi qichishish yengildan og'irgacha bo'lishi mumkin.

Homiladorlik xolestazi tashxisini qo'yish uchun jigar funksiyasi testini va zardobdai safro kislotasi testini talab qilish kerak. Ba'zi hollarda ALT darajasi ko'tarilishi mumkin bo'lsa-da, homimladorlik xolestazi bo'lgan ayollarning 20% har doim jigar funksiyasi testida normal ko'rsatkichlarga ega bo'ladi[19].Kaftlar va oyoqlarning qichishi yuqori safro kislotasi darajasi bilan kelganda homiladorlik xolestazining potensial diagnostikasi sifatida ko'rilishi mumkin (ammo bunday bemorlarida jigar funksional testi natijalari har doim ham ko'tarilmaydi). Homildorlik xolestazi uchun qon zardobidagi safro kislotasi qon testi safro kislotalarining miqdoriy o'lchovidir.

Homiladorlik davrida yuzaga keladigan jigar bilan bog'liq boshqa muammolarni davolovchi shifokor ko'rib chiqishi kerak. Bularga preeklampsiya, HELLP sindromi va homiladorlikdagi o'tkir yog'li gepatoz kiradi. Bundan tashqari, gepatitning boshqa sabablari, masalan, gepatit viruslari, saraton va ba'zi dorilar ta'sirinini ham hisobga olish kerak.

Davolash[tahrir | manbasini tahrirlash]

Ko'pgina shifokorlar ursodeoksixol kislotani buyuradilar. Eng so'nggi sinov, PITCHES[20], umumiy foydali ta'sir ko'rsatmadi, ammo ba'zi tadqiqotchilar safro kislotalari > 40 mkmol / litr bo'lgan ayollarga ursodeoksixolatni buyurish foydali bo'lishi mumkin deb hisoblashadi. homiladorlik xolestazi uchun hech qanday aniq davo choralari mavjud emas va muvaffaqiyatli natijani kafolatlashning hech qanday usuli yo'q bo'lsa-da, tadqiqotlar ursodeoksixol kislotasini qo'llash homila va onaning natijasini biroz yaxshiroq ko'rsatdi, xolestiramin esa faqat qichishishni yengillashtiradi[10][21].

Og'iz orqali suvda eriydigan K vitamini berish tug'ruq paytida qon ketish xavfini oldini olishga yordam berishi haqida hech qanday isbotlangan dalillar yo'q. Biroq, agar ayolda najas rangi oqargan bo'lsa, o'ta og'ir homiladorlik xolestazi (safro kislotalari > 100 mkmol/litr) bo'lsa yoki qon ivishi bilan bog'liq muammo bo'lsa, mutaxassislar homiladorlik xolestazi uchun bu usulni buyurishadi.

34-haftadan keyin tug'ilish o'lik tug'ilish xavfini kamaytirish uchun muhim bo'lishi mumkin, chunki yaqinda o'tkazilgan tadqiqot o'lik tug'ilish xavfi ortib borishida safro kislotalari darajasining bog'liqligini aniqladi. "The Lancet" jurnalida chop etilgan ushbu tadqiqot shuni ko'rsatadiki, homiladorlik bilan kasallangan ayollarning taxminan 90% i homiladorlikning 39 xaftaligigacha borishi mumkin. Biroq, bu natijalar tez qaytariladigan muntazam safro kislotasi sinovi natijalariga tayanadi[22].

Davolanmaganda asoratlanish xavfi[tahrir | manbasini tahrirlash]

Onada yuzaga keladigan asoratlarga quyidagilar kiradi:

  • Qichishish, kuchli va darmonsizlantiruvchi bo'lishi mumkin
  • Safro kislotalari 40 mkmol/litr dan oshganda spontan erta tug'ilish[23]

Homilada yuzaga keladigan asoratlarga quyidagilar kiradi:

  • Homila distressi
  • Mekoniyni yutish
  • O'lik tug'ilish

Ko'pgina hollarda bolani dunyoga keltirish odatda 34 dan 39 haftagacha tavsiya etiladi[22][24][25][26][27][28].

Qo'shma Shtatlarda ba'zi tadqiqotchilar, agar tug'ilish 36 haftada sodir bo'lsa, o'lik tug'ilish xavfi kamroq bo'lishini taklif qilishdi. Ovadianing tadqiqoti boshqacha fikr bildirsa-da[22], shuni ta'kidlash kerakki, Qo'shma Shtatlarda o't kislotasi testlari natijalari olinishi uchun yetti kungacha vaqt ketishi mumkin va bu shuni anglatadiki, tug'ruq vaqtini AQSh tadqiqotiga asoslash yanada oqilona bo'lishi mumkin[29].

Havolalar[tahrir | manbasini tahrirlash]

Manbalar[tahrir | manbasini tahrirlash]

  1. ↑ Rapini, Ronald P.. Dermatology: 2-Volume Set. St. Louis: Mosby, 2007. ISBN 978-1-4160-2999-1. 
  2. ↑ "Common skin conditions during pregnancy". American Family Physician 75 (2): 211–8. January 2007. PMID 17263216. 
  3. ↑ Kenyon, AP; Tribe, RM; Nelson-Piercy, C; Girling, JC; Williamson, C; Seed, PT; Vaughn-Jones, S; Shennan, AH (2010). "Pruritus in pregnancy: A study of anatomical distribution and prevalence in relation to the development of obstetric cholestasis". Obstetric Medicine 3 (1): 25–29. doi:10.1258/om.2010.090055. PMID 27582836. PMC 4989767. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4989767. 
  4. ↑ „Intrahepatic cholestasis of pregnancy“ (english). www.marchofdimes.org. Qaraldi: 2022-yil 27-aprel.
  5. ↑ Dixon, PH; Wadsworth, CA; Chambers, J; Donnelly, J; Cooley, S; Buckley, R; Mannino, R; Jarvis, S et al. (2014). "A comprehensive analysis of common genetic variation around six candidate loci for intrahepatic cholestasis of pregnancy". American Journal of Gastroenterology 109 (1): 76–84. doi:10.1038/ajg.2013.406. PMID 24366234. PMC 3887577. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3887577. 
  6. ↑ Dixon, PH; Sambrotta, M; Chambers, J; Taylor-Harris, P; Syngelaki, A; Nicolaides, K; Knisely, AS; Thompson, RJ et al. (2017). "An expanded role for heterozygous mutations of ABCB4, ABCB11, ATP8B1, ABCC2 and TJP2 in intrahepatic cholestasis of pregnancy". Scientific Reports 7 (1): 11823. doi:10.1038/s41598-017-11626-x. PMID 28924228. PMC 5603585. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5603585. 
  7. ↑ 7,0 7,1 "Intrahepatic cholestasis of pregnancy". Orphanet Journal of Rare Diseases 2: 26. 2007. doi:10.1186/1750-1172-2-26. PMID 17535422. PMC 1891276. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1891276. 
  8. ↑ 8,0 8,1 8,2 "Intrahepatic cholestasis of pregnancy: molecular pathogenesis, diagnosis and management". J. Hepatol. 33 (6): 1012–21. December 2000. doi:10.1016/S0168-8278(00)80139-7. PMID 11131439. 
  9. ↑ "Intrahepatic cholestasis of pregnancy in twin pregnancies". Journal of Hepatology 9 (1): 84–90. July 1989. doi:10.1016/0168-8278(89)90079-2. PMID 2768798. https://archive.org/details/sim_journal-of-hepatology_1989-07_9_1/page/84. 
  10. ↑ 10,0 10,1 "Bile acids and progesterone metabolites in intrahepatic cholestasis of pregnancy". Annals of Medicine 32 (2): 94–106. March 2000. doi:10.3109/07853890009011758. PMID 10766400. https://archive.org/details/sim_annals-of-medicine_2000-03_32_2/page/94. 
  11. ↑ Abu-Hayyeh, S (2015). "Prognostic and mechanistic potential of progesterone sulfates in intrahepatic cholestasis of pregnancy and pruritus gravidarum". Hepatology 63 (4): 1287–1298. doi:10.1002/hep.28265. PMID 26426865. PMC 4869673. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4869673. 
  12. ↑ Abu-Hayyeh, S; Ovadia, C; Lieu, T; Jensen, DD; Chambers, J; Dixon, PH; Lovgren-Sandblom, A; Bolier, R et al. (2016). "Prognostic and mechanistic potential of progesterone sulfates in intrahepatic cholestasis of pregnancy and pruritus gravidarum". Hepatology 63 (4): 1287–1298. doi:10.1002/hep.28265. PMID 26426865. PMC 4869673. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4869673. 
  13. ↑ Dixon, PH (2017). "An expanded role for heterozygous mutations of ABCB4, ABCB11, ATP8B1, ABCC2 and TJP2 in intrahepatic cholestasis of pregnancy". Scientific Reports 7 (1): 11823. doi:10.1038/s41598-017-11626-x. PMID 28924228. PMC 5603585. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5603585. 
  14. ↑ "Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver". Gastroenterology 118 (2): 422–30. 2000. doi:10.1016/S0016-5085(00)70224-1. PMID 10648470. https://archive.org/details/sim_gastroenterology_2000-02_118_2/page/422. 
  15. ↑ "Role of multidrug resistance P-glycoproteins in cholesterol esterification". Journal of Biological Chemistry 272 (2): 1026–31. January 1997. doi:10.1074/jbc.272.2.1026. PMID 8995398. 
  16. ↑ Williamson, Catherine; Geenes, Victoria (2014). "Intrahepatic cholestasis of pregnancy". Obstetrics and Gynecology 124 (1): 120–33. doi:10.1097/AOG.0000000000000346. PMID 24901263. https://semanticscholar.org/paper/98b5c92eb0694656c11e8fa0ae32f2e850b743c5. 
  17. ↑ Ovadia, Caroline; Williamson, Catherine (2016). "Intrahepatic cholestasis of pregnancy: recent advances". Clinics in Dermatology 34 (3): 327–34. doi:10.1016/j.clindermatol.2016.02.004. PMID 27265070. https://kclpure.kcl.ac.uk/portal/en/publications/intrahepatic-cholestasis-of-pregnancy(b96ae410-b8c6-4877-b145-399bc7580718).html. 
  18. ↑ "Low serum selenium concentration and glutathione peroxidase activity in intrahepatic cholestasis of pregnancy". British Medical Journal (Clinical Research Edition) 294 (6565): 150–2. January 1987. doi:10.1136/bmj.294.6565.150. PMID 3109544. PMC 1245162. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1245162. 
  19. ↑ Conti-Ramsden, F; McEwan, M; Hill, R; Wade, J; Abraham, G; Buckeldee, O; Williamson, C; Knight, CL et al. (2019). "Detection of additional abnormalities or co-morbidities in women with suspected intrahepatic cholestasis of pregnancy". Obstetric Medicine 13 (4): 185–191. doi:10.1177/1753495X19868873. PMID 33343695. PMC 7726172. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=7726172. 
  20. ↑ Chappell, LC; Chambers, J; Dixon, PH; Dorling, J; Hunter, R; Bell, JL; Bowler, U; Hardy, P et al. (2019). "Ursodeoxycholic acid versus placebo in the treatment of women with intrahepatic cholestasis of pregnancy (ICP) to improve perinatal outcomes: protocol for a randomised controlled trial (PITCHES)". Lancet 394 (10201): 849–860. doi:10.1016/S0140-6736(19)31270-X. PMID 31378395. PMC 6739598. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=6739598. 
  21. ↑ Walker, Kate F.; Chappell, Lucy C.; Hague, William M.; Middleton, Philippa; Thornton, Jim G. (27 July 2020). "Pharmacological interventions for treating intrahepatic cholestasis of pregnancy". The Cochrane Database of Systematic Reviews 2020 (7): CD000493. doi:10.1002/14651858.CD000493.pub3. ISSN 1469-493X. PMID 32716060. PMC 7389072. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=7389072. 
  22. ↑ 22,0 22,1 22,2 Ovadia, Caroline (2019). "Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses". Lancet 393 (10174): 899–909. doi:10.1016/S0140-6736(18)31877-4. PMID 30773280. PMC 6396441. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=6396441. 
  23. ↑ Glantz, A; Marschall, HU; Mattsson, LA (2004). "Intrahepatic cholestasis of pregnancy: Relationships between bile acid levels and fetal complication rates". Hepatology 40 (2): 467–474. doi:10.1002/hep.20336. PMID 15368452. https://archive.org/details/sim_hepatology_2004-08_40_2/page/467. 
  24. ↑ Geenes V, Williamson C (2009). "Intrahepatic Cholestasis of pregnancy". World Journal of Gastroenterology 15 (17): 2049–2066. doi:10.3748/wjg.15.2049. PMID 19418576. PMC 2678574. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2678574. 
  25. ↑ Fisk NM, Storey GN: "Fetal outcome in obstetric cholestasis. Br J Obstet Gynaec 1988;95:1137- 1143.
  26. ↑ Zecca E, Costa S, Lauriola V (2003). "Bile acid pneumonia: A "new" form of neonatal respiratory distress syndrome?". Pediatrics 114 (1): 269–272. doi:10.1542/peds.114.1.269. PMID 15231944. 
  27. ↑ Shaw D, Frohlich J, Wittmann BA, Willms M (1982). "A prospective study of 18 patients with cholestasis of pregnancy". Am J Obstet Gynecol 142 (6): 621–625. doi:10.1016/s0002-9378(16)32430-9. PMID 7065033. 
  28. ↑ Davies MH, Silva RC, Jones SR (1995). "Fetal mortality associated with cholestasis of pregnancy and the potential benefit of therapy with ursodeoxycholic acid". Gut 37 (4): 580–584. doi:10.1136/gut.37.4.580. PMID 7489950. PMC 1382915. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1382915. 
  29. ↑ Puljic A, Kim E, Page J (2015). "The risk of infant and fetal death by each additional week of expectant management in intrahepatic cholestasis of pregnancy by gestational age". Am J Obstet Gynecol 212 (5): 667.e1–5. doi:10.1016/j.ajog.2015.02.012. PMID 25687562.  
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