{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T06:24:13Z","timestamp":1787293453970,"version":"build-2736575974"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Severe early-onset pregnancy-associated cholestasis with atypical features may reflect an intrahepatic cholestasis of pregnancy (ICP) component superimposed on underlying hepatobiliary disease. Evidence for bicyclol use during pregnancy is very limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>A 34-year-old pregnant woman, developed palmoplantar pruritus and severe cholestasis at 15\u00a0weeks of gestation. She had previously undergone cholecystectomy and common bile duct exploration. The working diagnosis was pregnancy-associated cholestasis with a possible ICP component superimposed on suspected chronic hepatobiliary dysfunction. Biochemical abnormalities persisted despite treatment with ursodeoxycholic acid, ademetionine, glutathione, and polyene phosphatidylcholine. Off-label bicyclol at 50\u00a0mg three times daily was added at 29\u00a0weeks and continued for approximately 5\u00a0weeks. Before bicyclol was added, alanine aminotransferase (ALT) level ranged from 724 to 1,492\u00a0U\/L, and total bile acids (TBA) level ranged from 111.2 to 224.6\u00a0\u03bcmol\/L. Following bicyclol initiation, ALT ranged from 137 to 464\u00a0U\/L. TBA remained markedly elevated, ranging from 96.7 to 146.6\u00a0\u03bcmol\/L. Total bilirubin ranged from 42.8 to 46.5\u00a0\u03bcmol\/L. Overall, aminotransferase levels were lower than the pretreatment range, whereas TBA and total bilirubin remained markedly elevated. Cesarean delivery was performed at 34+1\u00a0weeks of gestation because of worsening maternal symptoms and persistent hyperbilirubinemia. Grade III meconium-stained amniotic fluid was noted during surgery. A liveborn female infant was delivered with Apgar scores of 10, 10, and 10\u00a0at 1, 5, and 10\u00a0min, respectively. No early neonatal complications were observed. At 42\u00a0days postpartum, liver tests remained mildly abnormal, which suggested persistent hepatobiliary dysfunction rather than cholestasis limited to pregnancy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A temporal association was observed between bicyclol initiation and lower aminotransferase levels. However, this temporal association should not be interpreted as evidence of causality because multiple factors, including substantial pretreatment biochemical variability, concomitant multidrug therapy, advancing gestation, and possible underlying hepatobiliary disease, may have contributed to the observed changes. This case does not establish efficacy, pregnancy prolongation, or maternal and fetal safety. Instead, it provides a hypothesis-generating observation and highlights the need for further structural and genetic evaluation and systematic studies with long-term infant follow-up.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1874712","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T05:37:07Z","timestamp":1787290627000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Temporal association between adjunctive bicyclol initiation and discordant biochemical trends in severe early-onset pregnancy-associated cholestasis: a Case Report"],"prefix":"10.3389","volume":"17","author":[{"given":"Chun-Fei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1016\/S0140-6736(19)31270-X","article-title":"Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES): a randomised controlled trial","volume":"394","author":"Chappell","year":"2019","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/s41572-025-00633-2","article-title":"Intrahepatic cholestasis of pregnancy","volume":"11","author":"Dajti","year":"2025","journal-title":"Nat. Rev. Dis. Prim."},{"key":"B3","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1016\/j.jhep.2023.03.006","article-title":"EASL clinical practice guidelines on the management of liver diseases in pregnancy","volume":"79","year":"2023","journal-title":"J. Hepatol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.jhep.2024.04.006","article-title":"EASL clinical practice guidelines on genetic cholestatic liver diseases","volume":"81","year":"2024","journal-title":"J. Hepatol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e95","DOI":"10.1111\/1471-0528.17206","article-title":"Royal College of Obstetricians and Gynaecologists. Intrahepatic cholestasis of pregnancy: Green-top Guideline No. 43 June 2022","volume":"12","author":"Girling","year":"2022","journal-title":"BJOG"},{"key":"B5","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1111\/j.1478-3231.2005.01103.x","article-title":"Mechanism of protective action of bicyclol against CCl4-induced liver injury in mice","volume":"25","author":"Liu","year":"2005","journal-title":"Liver Int."},{"key":"B6","doi-asserted-by":"publisher","first-page":"177381","DOI":"10.1016\/j.ejphar.2025.177381","article-title":"Expanding the Horizons of bicyclol in multiple diseases: mechanisms, therapeutic implications and challenges","volume":"993","author":"Liu","year":"2025","journal-title":"Eur. J. Pharmacol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2654","DOI":"10.1002\/hep4.2051","article-title":"Clinical phenotype of adult-onset liver disease in patients with variants in ABCB4, ABCB11, and ATP8B1","volume":"6","author":"Nayagam","year":"2022","journal-title":"Hepatol. Commun."},{"key":"B8","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1016\/S0140-6736(18)31877-4","article-title":"Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses","volume":"393","author":"Ovadia","year":"2019","journal-title":"Lancet"},{"key":"B9","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/S2468-1253(21)00074-1","article-title":"Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a systematic review and individual participant data meta-analysis","volume":"6","author":"Ovadia","year":"2021","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"97","DOI":"10.4174\/jkss.2012.83.2.97","article-title":"Common bile duct dilatation after cholecystectomy: a one-year prospective study","volume":"83","author":"Park","year":"2012","journal-title":"J. Korean Surg. Soc."},{"key":"B11","doi-asserted-by":"publisher","first-page":"B2","DOI":"10.1016\/j.ajog.2020.11.002","article-title":"Society for maternal-fetal medicine consult series #53: intrahepatic cholestasis of pregnancy: replaces consult #13, April 2011","volume":"224","author":"Lee","year":"2021","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1111\/liv.15290","article-title":"Efficacy and safety of bicyclol for treating patients with idiosyncratic acute drug-induced liver injury: a multicenter, randomized, phase II trial","volume":"42","author":"Tang","year":"2022","journal-title":"Liver Int."},{"key":"B13","doi-asserted-by":"publisher","first-page":"CD000493","DOI":"10.1002\/14651858.CD000493.pub3","article-title":"Pharmacological interventions for treating intrahepatic cholestasis of pregnancy","volume":"7","author":"Walker","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"B14","doi-asserted-by":"publisher","first-page":"107308","DOI":"10.1016\/j.intimp.2020.107308","article-title":"Therapeutic potential of bicyclol in liver diseases: lessons from a synthetic drug based on herbal derivative in traditional Chinese medicine","volume":"91","author":"Zhao","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/s41420-022-01173-4","article-title":"Regulating Nrf2-GPx4 axis by bicyclol can prevent ferroptosis in carbon tetrachloride-induced acute liver injury in mice","volume":"8","author":"Zhao","year":"2022","journal-title":"Cell Death Discov."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1874712\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T05:37:07Z","timestamp":1787290627000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1874712\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":16,"alternative-id":["10.3389\/fphar.2026.1874712"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1874712","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,21]]},"article-number":"1874712"}}