{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T21:26:27Z","timestamp":1785273987505,"version":"3.55.0"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"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. Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Hepatopulmonary syndrome (HPS) is a rare complication of metabolic associated fatty liver disease (MAFLD) occurring subsequent to hypopituitarism, often developing after resection of hypothalamic or pituitary tumors. The aim of this study is to report an illustrative case of an HPS patient who was successfully treated with growth hormone replacement therapy, without liver transplantation which is conventionally regarded as the only treatment option. Additionally, we conducted a comprehensive review of published case reports of HPS in the pediatric population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We systematically searched literature databases to identify case reports and case series of HPS associated with hypopituitarism diagnosed in childhood. The search included MEDLINE\/PubMed, Scopus, Embase, and Google Scholar from 1990 to 2023. The review process adhered to the PRISMA checklist for comprehensive reporting and methodological transparency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>An 18-year-old female, who had been followed up for MAFLD after craniopharyngioma resection, presented with cyanosis and progressive dyspnea. She was diagnosed with severe degree of HPS. The patient began treatment with recombinant human growth hormone, leading to a significant improvement in respiratory symptoms within 3 months, and normalization of lung shunt ratio after 6 months of therapy. In our systematic review, nine patients from nine studies across six countries were identified. The median age at diagnosis of hypopituitarism was 10.5 years (range 1\u201316 years), and HPS was diagnosed at a median interval of 7 years later (range 0\u201326 years). Half of the patients had not received growth hormone therapy after being diagnosed with hypopituitarism, which subsequently led to the diagnosis of HPS. Three patients underwent liver transplantation, but non-alcoholic steatohepatitis recurred in all cases. Six patients were successfully treated with growth hormone replacement therapy without undergoing liver transplantation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>HPS can occur in pediatric patients with MAFLD who have undergone resection of the tumor in the hypothalamus or pituitary gland. Our findings suggest that growth hormone replacement therapy can be a possible alternative to liver transplantation for HPS patients. However, further investigations need to be performed to validate the efficacy of growth hormone treatment in different causes of HPS cases.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2024.1407686","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T04:28:08Z","timestamp":1729571288000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Hepatopulmonary syndrome secondary to metabolic associated fatty liver disease in childhood \u2014 novel treatment with growth hormone replacement therapy: a case report and systematic review of literature"],"prefix":"10.3389","volume":"15","author":[{"given":"Yunsoo","family":"Choe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Jeong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Ah","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Sung","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choong Ho","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0707185","article-title":"Hepatopulmonary syndrome\u2013a liver-induced lung vascular disorder","volume":"358","author":"Rodr\u00edguez-Roisin","year":"2008","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v10.i18.6211","article-title":"Growth hormone ameliorates Hepatopulmonary syndrome and nonalcoholic steatohepatitis secondary to hypopituitarism in a child: A case report","volume":"10","author":"Zhang","year":"2022","journal-title":"World J Clin Cases"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.6065\/apem.2018.23.1.51","article-title":"Hepatopulmonary syndrome caused by hypothalamic obesity and nonalcoholic fatty liver disease after surgery for craniopharyngioma: A case report","volume":"23","author":"Jung","year":"2018","journal-title":"Ann Pediatr Endocrinol Metab"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3046.2007.00767.x","article-title":"Recurrence of non-alcoholic steatohepatitis after liver transplantation in a 13-yr-old boy","volume":"11","author":"Jankowska","year":"2007","journal-title":"Pediatr Transplant"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2021-244805","article-title":"Hepatopulmonary syndrome as the first and only manifestation of cirrhosis in a patient with hypopituitarism","volume":"14","author":"Alabsawy","year":"2021","journal-title":"BMJ Case Rep"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v9.i18.4852","article-title":"Growth hormone cocktail improves hepatopulmonary syndrome secondary to hypopituitarism: A case report","volume":"9","author":"Ji","year":"2021","journal-title":"World J Clin Cases"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.5223\/kjpgn.2010.13.1.51","article-title":"Nonalcoholic fatty liver disease in children with hypopituitarism","volume":"13","author":"Yoon","year":"2010","journal-title":"Korean J Pediatr Gastroenterol Nutr"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.235.61","article-title":"Long-term survival with growth hormone replacement after liver transplantation of pediatric nonalcoholic steatohepatitis complicating acquired hypopituitarism","volume":"235","author":"Fujio","year":"2015","journal-title":"Tohoku J Exp Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e3181a1c496","article-title":"Rapid progression from Hepatopulmonary syndrome to portopulmonary hypertension in an adolescent female with hypopituitarism","volume":"50","author":"Justino","year":"2010","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.0027-17","article-title":"Hormone-replacement therapy for Hepatopulmonary syndrome and nash associated with hypopituitarism","volume":"57","author":"Torii","year":"2018","journal-title":"Intern Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/(ISSN)1527-6473","article-title":"Rapid recurrence of nonalcoholic fatty liver disease after transplantation in a child with hypopituitarism and Hepatopulmonary syndrome","volume":"11","author":"Jonas","year":"2005","journal-title":"Liver Transpl"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1378\/chest.72.3.305","article-title":"Exercise-aggravated hypoxemia and orthodeoxia in cirrhosis","volume":"72","author":"Kennedy","year":"1977","journal-title":"Chest"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v13.i11.1699","article-title":"Hepatopulmonary syndrome: an update","volume":"13","author":"Gandhi","year":"2021","journal-title":"World J Hepatol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2011.00060","article-title":"Hypothalamic obesity after craniopharyngioma: mechanisms, diagnosis, and treatment","volume":"2","author":"Lustig","year":"2011","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021797","article-title":"Obesity in patients with craniopharyngioma: assessment of food intake and movement counts indicating physical activity","volume":"88","author":"Harz","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.hepres.2005.09.024","article-title":"The role of leptin in progression of non-alcoholic fatty liver disease","volume":"33","author":"Ikejima","year":"2005","journal-title":"Hepatol Res"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/cen.14344","article-title":"Effect of recombinant human growth hormone on liver fat content in young adults with nonalcoholic fatty liver disease","volume":"94","author":"Pan","year":"2021","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.6065\/apem.2244046.023","article-title":"The effect of hypothalamic involvement and growth hormone treatment on cardiovascular risk factors during the transition period in patients with childhood-onset craniopharyngioma","volume":"28","author":"Park","year":"2023","journal-title":"Ann Pediatr Endocrinol Metab"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18071447","article-title":"The role of growth hormone and insulin-like growth factor-I in the liver","volume":"18","author":"Takahashi","year":"2017","journal-title":"Int J Mol Sci"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0140189","article-title":"Accelerated telomere shortening in acromegaly; Igf-I induces telomere shortening and cellular senescence","volume":"10","author":"Matsumoto","year":"2015","journal-title":"PloS One"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac088","article-title":"Growth hormone and insulin-like growth factor 1 regulation of nonalcoholic fatty liver disease","volume":"107","author":"Dichtel","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/670139","article-title":"Pharmacological treatment for Hepatopulmonary syndrome","volume":"2013","author":"Eshraghian","year":"2013","journal-title":"BioMed Res Int"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000002300","article-title":"Growth hormone therapy in decompensated cirrhosis: an open-label, randomized control trial","volume":"119","author":"Kumari","year":"2024","journal-title":"Am J Gastroenterol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"58","DOI":"10.14341\/probl.2021675","article-title":"[Hepatopulmonary syndrome: A rare manifestation of cirrhosis in patient with diencephalic obesity and nonalcoholic fatty liver disease after surgery for craniopharyngioma]","volume":"67","author":"Mazerkina","year":"2021","journal-title":"Probl Endokrinol (Mosk)"},{"key":"B25","doi-asserted-by":"publisher","first-page":"4134","DOI":"10.1038\/s41598-021-83785-x","article-title":"Clinical outcomes and risk factors of Hepatopulmonary syndrome in children","volume":"11","author":"Kim","year":"2021","journal-title":"Sci Rep"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2024.1407686\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T04:28:11Z","timestamp":1729571291000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2024.1407686\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,22]]},"references-count":25,"alternative-id":["10.3389\/fendo.2024.1407686"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2024.1407686","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,22]]},"article-number":"1407686"}}