{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:03:06Z","timestamp":1767225786663,"version":"3.48.0"},"reference-count":18,"publisher":"American Academy of Pediatrics (AAP)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:p>A 13-year-old girl presented for evaluation of pulmonary hypertension after symptoms of dyspnea and exercise intolerance. Full evaluation was negative except for abdominal ultrasonography with splenomegaly and esophageal varices suggestive of portal hypertension. Cardiac and hepatic vein catheterization confirmed portopulmonary hypertension. Liver biopsy demonstrated sinusoidal dilatation, nodularity, and minimal fibrosis, which was interpreted as possible nodular regenerative hyperplasia but not cirrhosis. Radiographic imaging, including computed tomography venography, demonstrated an elongated and severely stenotic extrahepatic portal vein, and portal hypertension was presumed to be secondary to congenital portal vein hypoplasia. She was treated with ambrisentan with initial improvement in symptoms and estimated pulmonary pressure. Whole-exome sequencing revealed a likely pathogenic missense mutation in Delta-like canonical Notch ligand 4 associated with Adams-Oliver syndrome. After 2\u00a0years, pulmonary hypertension and right heart failure symptoms worsened, along with liver failure. She then had fulminant liver failure and cardiorespiratory arrest. Resuscitative efforts included extracorporeal membranous oxygenation (ECMO), but because of hypoxic brain injury, care was compassionately withdrawn. Autopsy limited to the thorax and abdomen revealed high-grade pulmonary plexiform arteriopathy, splenomegaly, esophageal varices, and large splenorenal shunt. The liver was small with a nodular surface but not fibrotic. The entire length of the extrahepatic portal vein was severely stenotic, and intrahepatic portal veins were missing or diminutive\u2014findings diagnostic of hepatoportal sclerosis. Noncirrhotic portopulmonary hypertension is rare and should include evaluation of immunologic, infectious, toxic, thrombotic, and genetic etiologies. Unfortunately, there is no known treatment of hepatoportal sclerosis.<\/jats:p>","DOI":"10.1542\/peds.2025-073243","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:02:20Z","timestamp":1766016140000},"source":"Crossref","is-referenced-by-count":0,"title":["Noncirrhotic Portopulmonary Hypertension Due to Hepatoportal Sclerosis in Adams-Oliver Syndrome"],"prefix":"10.1542","volume":"157","author":[{"given":"Jennifer","family":"Merk","sequence":"first","affiliation":[{"name":"1University of Washington, Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delphine","family":"Yung","sequence":"additional","affiliation":[{"name":"1University of Washington, Seattle, Washington"},{"name":"2Seattle Children\u2019s Hospital, Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason N.","family":"Wright","sequence":"additional","affiliation":[{"name":"1University of Washington, Seattle, Washington"},{"name":"2Seattle Children\u2019s Hospital, Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raj P.","family":"Kapur","sequence":"additional","affiliation":[{"name":"1University of Washington, Seattle, Washington"},{"name":"2Seattle Children\u2019s Hospital, Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"417","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"issue":"9","key":"2025123118590161800_r1","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/jhg.2017.48","article-title":"Novel missense mutation in DLL4 in a Japanese sporadic case of Adams-Oliver syndrome","volume":"62","author":"Nagasaka","year":"2017","journal-title":"J Hum Genet."},{"issue":"1","key":"2025123118590161800_r2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1093\/oxfordjournals.jhered.a105415","article-title":"Hereditary deformities in man: due to arrested development","volume":"36","author":"Adams","year":"1945","journal-title":"J Hered."},{"issue":"3","key":"2025123118590161800_r3","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1002\/ajmg.a.37889","article-title":"Adams-Oliver syndrome review of the literature: refining the diagnostic phenotype","volume":"173","author":"Hassed","year":"2017","journal-title":"Am J Med Genet A."},{"issue":"21","key":"2025123118590161800_r4","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1161\/CIR.0000000000000329","article-title":"Pediatric pulmonary hypertension: guidelines from the American Heart Association and American Thoracic Society","volume":"132","author":"Abman","year":"2015","journal-title":"Circulation."},{"issue":"6","key":"2025123118590161800_r5","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1053\/j.semdp.2019.07.006","article-title":"Idiopathic noncirrhotic portal hypertension","volume":"36","author":"Fiel","year":"2019","journal-title":"Semin Diagn Pathol."},{"issue":"3","key":"2025123118590161800_r6","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.gastha.2023.01.003","article-title":"Hepatoportal sclerosis - 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