Reply to: “Intrahepatic cholestasis of pregnancy: An under recognised complication of maternal NAFLD?”

We thank Drs Phillips and Senaratne for their inquiry about the potential association of non-alcoholic fatty liver disease (NAFLD) in pregnancy with intrahepatic cholestasis (ICP) our study cohort.[1]Sarkar M. Grab J. Dodge J.L. Gunderson E.P. Rubin Irani R.A. et al.Non-alcoholic is associated adverse maternal perinatal outcomes.J Hepatol. 2020; 73: 516-522Abstract Full Text PDF PubMed Scopus (13) Google Scholar ICP a common pregnancy-specific that marked by pruritus elevated bile acids. Prospective studies evaluating NAFLD are lacking, retrospective data subject to “confounding indication” whereby may be coincidentally detected on imaging during an evaluation ICP-related enzyme elevation. metabolic changes pregnancy. indicate increases risk incident gestational diabetes, higher triglyceride levels, lower high-density lipoprotein levels pregnancy.[2]Martineau M.G. Raker C. Dixon P.H. Chambers Machirori King N.M. al.The profile impaired glucose tolerance, dyslipidemia, increased fetal growth.Diabetes Care. 2015; 38: 243-248Crossref (67) These result from downregulation acid receptors TGR5 farnesoid X receptor context ICP, which turn influences lipid homeostasis.3Van Mil S.W. Milona A. Mullenbach R. Geenes V.L. al.Functional variants central sensor FXR identified pregnancy.Gastroenterology. 2007; 133: 507-516Abstract (178) Scholar, 4Abu-Hayyeh S. Papacleovoulou G. Lovgren-Sandblom Tahir Oduwole O. Jamaludin N.A. al.Intrahepatic sulfated progesterone metabolites inhibit resulting cholestatic phenotype.Hepatology. 2013; 57: 716-726Crossref (97) 5Bellafante E. McIlvride Nikolova V. Fan H.M. Manna L.B. al.Maternal homeostasis mouse models cholestasis.Sci Rep. 10: 11523Crossref (5) However, mechanism pre-existing could increase not clear. In response Senaratne's inquiry, we evaluated whether having was utilizing ICD 9 10 codes diagnosis. Importantly, lacks specific code falls under description “Liver biliary tract disorders pregnancy”, thus other diseases also captured. With this caveat mind, did identify proportion pregnancies group (22.3%) compared chronic (13.0%) or without (0.3%), p values <0.001. Comparing vs. (including conditions) both univariate analysis (odds ratio [OR] 2.1; 95% CI 1.8–2.5, <0.001) multivariate analyses (OR 1.4; 1.1–1.7; adjusting age, race, multiple gestation, pre-pregnancy obesity, dyslipidemia hypertension. Estimates remained stable further adjustment diabetes 1.3; 1.1–1.6; <0.001). Thus, there does appear between cohort, but reflects biologically plausible relationship remains determined. Moreover, these results should interpreted caution light non-specific coding used define ICP. findings do support need prospective evaluate conversely, known ICP-associated profiles influence natural history following delivery. MS supported K23 award National Institutes Health ( DK111944 ). M.S. developed concept, design, primary manuscript draft. J.G. analyzed provided content review edits. R.I The authors declare no conflicts interest pertain work. Please refer accompanying ICMJE disclosure forms details. Download .pdf (.16 MB) Help pdf files disclosures.pdf Intrahepatic pregnancy: An recognised complication NAFLD?Journal HepatologyVol. 74Issue 3PreviewWe read article “Non-alcoholic outcomes” published September 2020 issue Journal Hepatology.1 As tertiary referral centre obstetric care Western Australia, have seen increasing rates obesity over last decade. Full-Text Non-alcoholic outcomesJournal 73Issue 3PreviewThe prevalence rising young adults, implications reproductive-aged women. Whether confers more serious risks health unclear.