{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T11:09:29Z","timestamp":1782731369227,"version":"3.54.5"},"reference-count":26,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T00:00:00Z","timestamp":1697587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["TL1TR002555"],"award-info":[{"award-number":["TL1TR002555"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013554","name":"Foundation for Women and Girls with Blood Disorders","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["K12HD103083"],"award-info":[{"award-number":["K12HD103083"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objective<\/jats:title>\n<jats:p>Hepatitis C virus and intrahepatic cholestasis of pregnancy (ICP) are well-known independent risk factors for adverse outcomes in pregnancy. In addition, it is well-established that there is an association between Hepatitis C and ICP. This study\u2019s objective was to describe the impact of having both Hepatitis C and ICP on maternal and obstetric outcomes compared to patients having either Hepatitis C or ICP.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We conducted a retrospective cohort study of the Nationwide Readmissions Database, an all-payor sample of discharges from approximately 60% of US hospitalizations. Deliveries at 24\u201342+ weeks between 10\/2015 and 12\/2020 were included. Diagnosis of Hepatitis C and ICP, and outcomes related to severe maternal morbidity were identified using International Classification of Disease-10 codes. Patients were categorized based on Hepatitis C and ICP status. Weighted logistic and negative binomial regression analyses were used to evaluate the association between Hepatitis C and ICP status and outcomes, adjusting for patient and hospital characteristics. The primary outcome was any severe maternal morbidity; secondary outcomes included acute respiratory distress syndrome, acute kidney injury, sepsis, gestational diabetes, cesarean delivery, preterm birth, and hospital length of stay. We modeled interaction terms between ICP and Hepatitis C to assess whether there was a greater or lesser effect from having both conditions on outcomes than we would expect from additive combination of the individual components (<jats:italic>i<\/jats:italic>.<jats:italic>e<\/jats:italic>., synergy or antagonism).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>A total of 10,040,850 deliveries between 24\u201342+ weeks were identified. Of these, 45,368 had Hepatitis C only; 84,582 had ICP only; and 1,967 had both Hepatitis C and ICP. Patients with both Hepatitis C and ICP had 1.5-fold higher odds of developing severe maternal morbidity compared to having neither. There was an also an increased odds of severe maternal morbidity in patients with both Hepatitis C and ICP compared to patients with only Hepatitis C or ICP. Having both was also associated with higher odds of preterm birth and length of stay compared to having only Hepatitis C, only ICP, or neither (preterm birth: aOR 5.09, 95% CI 4.87\u20135.33 vs. neither; length of stay: 46% mean increase, 95% CI 35\u201358% vs. neither). Associations were additive\u2014no significant interactions between hepatitis C and cholestasis were found on rates of severe maternal morbidity, acute respiratory distress syndrome, acute kidney injury, sepsis, cesarean section, or preterm birth (all p&gt;0.05), and was minimal for gestational diabetes and length of stay.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Hepatitis C and ICP are independent, additive risk factors for adverse maternal and obstetric outcomes. Despite physiologic plausibility, no evidence of a synergistic effect of these two diagnoses on outcomes was noted. These data may be useful in counseling patients regarding their increased risk of adverse outcomes when ICP presents in association with Hepatitis C versus ICP alone.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0293030","type":"journal-article","created":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T17:34:15Z","timestamp":1697650455000},"page":"e0293030","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Maternal and neonatal outcomes in patients with hepatitis C and intrahepatic cholestasis of pregnancy: The sum of the parts"],"prefix":"10.1371","volume":"18","author":[{"given":"Emily C.","family":"Goins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren E.","family":"Wein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia Y.","family":"Watkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa I. K.","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Phillips","family":"Heine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenna L.","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah K.","family":"Dotters-Katz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0321-6280","authenticated-orcid":true,"given":"Jerome Jeffrey","family":"Federspiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,10,18]]},"reference":[{"issue":"5","key":"pone.0293030.ref001","doi-asserted-by":"crossref","first-page":"768","DOI":"10.2105\/AJPH.2021.306251","article-title":"Hepatitis C in the United States: One Step Forward, Two Steps Back","volume":"111","author":"CD Rio","year":"2021","journal-title":"Am J Public Health"},{"issue":"3","key":"pone.0293030.ref002","article-title":"Trends and Characteristics in Maternal Hepatitis C Virus Infection Rates During Pregnancy: United States, 2016\u20132021","volume":"73","author":"DM Ely","year":"2023","journal-title":"National Vital Statistics Reports"},{"issue":"2","key":"pone.0293030.ref003","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/s41575-020-00361-w","article-title":"Viral hepatitis and pregnancy","volume":"18","author":"NA Terrault","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"2","key":"pone.0293030.ref004","doi-asserted-by":"crossref","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":"Society for Maternal-Fetal Medicine","year":"2021","journal-title":"Am J Obstet Gynecol"},{"key":"pone.0293030.ref005","first-page":"6641023","article-title":"Intrahepatic Cholestasis of Pregnancy and Associated Adverse Maternal and Fetal Outcomes: A Retrospective Case-Control Study","volume":"2021","author":"M Luo","year":"2021","journal-title":"Gastroenterol Res Pract"},{"issue":"10174","key":"pone.0293030.ref006","doi-asserted-by":"crossref","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":"C Ovadia","year":"2019","journal-title":"Lancet"},{"issue":"1","key":"pone.0293030.ref007","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/s41598-023-27668-3","article-title":"Prevalence and factors associated with hepatitis C among pregnant women in China: a cross-sectional study","volume":"13","author":"S He","year":"2023","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0293030.ref008","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.clinre.2016.07.004","article-title":"Hepatitis C infection and intrahepatic cholestasis of pregnancy: A systematic review and meta-analysis","volume":"41","author":"K Wijarnpreecha","year":"2017","journal-title":"Clin Res Hepatol Gastroenterol"},{"issue":"4","key":"pone.0293030.ref009","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1097\/MEG.0000000000000293","article-title":"Intrahepatic cholestasis of pregnancy with concomitant hepatitis C virus infection, Joan C. Edwards SOM, Marshall University","volume":"27","author":"T Belay","year":"2015","journal-title":"Eur J Gastroenterol Hepatol"},{"issue":"4","key":"pone.0293030.ref010","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1136\/gut.2008.159541","article-title":"Contribution of variant alleles of ABCB11 to susceptibility to intrahepatic cholestasis of pregnancy","volume":"58","author":"PH Dixon","year":"2009","journal-title":"Gut"},{"key":"pone.0293030.ref011","unstructured":"Centers for Disease Control and Prevention. How does CDC identify severe maternal morbidity 2019 [updated December 26, 2019; cited 2023]. Available from: https:\/\/www.cdc.gov\/reproductivehealth\/maternalinfanthealth\/smm\/severe-morbidity-ICD.htm."},{"issue":"3","key":"pone.0293030.ref012","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1097\/AOG.0000000000004022","article-title":"An Expanded Obstetric Comorbidity Scoring System for Predicting Severe Maternal Morbidity","volume":"136","author":"SA Leonard","year":"2020","journal-title":"Obstet Gynecol"},{"key":"pone.0293030.ref013","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.ejogrb.2020.09.023","article-title":"Serological screening for hepatitis C during pregnancy: Seroprevalence and maternal and neonatal outcomes in 45,000 pregnant women","volume":"254","author":"S Piffer","year":"2020","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"issue":"9","key":"pone.0293030.ref014","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1002\/hep4.2002","article-title":"Hepatitis C is associated with more adverse pregnancy outcomes than hepatitis B: A 7-year national inpatient sample study","volume":"6","author":"B Chen","year":"2022","journal-title":"Hepatol Commun"},{"issue":"8","key":"pone.0293030.ref015","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1007\/s10995-023-03666-9","article-title":"Maternal Hepatitis C Virus Infection and Adverse Newborn Outcomes in the US","volume":"27","author":"RB Hood","year":"2023","journal-title":"Matern Child Health J"},{"issue":"6","key":"pone.0293030.ref016","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1097\/OGX.0000000000000442","article-title":"Hepatitis C in Pregnancy: Review of Current Knowledge and Updated Recommendations for Management","volume":"72","author":"CM Page","year":"2017","journal-title":"Obstet Gynecol Surv"},{"key":"pone.0293030.ref017","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.ejogrb.2020.11.052","article-title":"Viral Hepatitis in pregnancy","volume":"256","author":"VN Chilaka","year":"2021","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"pone.0293030.ref018","doi-asserted-by":"crossref","first-page":"154802","DOI":"10.1016\/j.metabol.2021.154802","article-title":"Molecular mechanisms underlying hepatitis C virus infection-related diabetes","volume":"121","author":"Y Ding","year":"2021","journal-title":"Metabolism"},{"issue":"10","key":"pone.0293030.ref019","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/S1701-2163(16)34680-1","article-title":"The prevalence of gestational diabetes mellitus and glucose abnormalities in pregnant women with hepatitis C virus infection in British Columbia","volume":"32","author":"MC Buresi","year":"2010","journal-title":"J Obstet Gynaecol Can"},{"issue":"7","key":"pone.0293030.ref020","doi-asserted-by":"crossref","first-page":"e394","DOI":"10.1111\/j.1365-2893.2011.01436.x","article-title":"Pregnancy outcomes associated with viral hepatitis","volume":"18","author":"KL Reddick","year":"2011","journal-title":"J Viral Hepat"},{"issue":"1","key":"pone.0293030.ref021","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.cld.2015.08.010","article-title":"New Insights on Intrahepatic Cholestasis of Pregnancy","volume":"20","author":"A Floreani","year":"2016","journal-title":"Clin Liver Dis"},{"key":"pone.0293030.ref022","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.ejogrb.2013.12.037","article-title":"Intrahepatic cholestasis of pregnancy is associated with an increased risk of gestational diabetes","volume":"176","author":"M Martineau","year":"2014","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"issue":"7","key":"pone.0293030.ref023","first-page":"791","article-title":"Acute renal insufficiency with secondary intraheptic cholestasis as a complication of pyelonephritis in pregnancy","volume":"46","author":"J Mlynarski","year":"1975","journal-title":"Ginkeologia 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