{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:04:28Z","timestamp":1789535068311,"version":"build-2803163510"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"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. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute respiratory distress syndrome (ARDS) and pancreatitis are fatal extrahepatic complication of hepatitis E virus (HEV)\u2013induced acute liver failure (ALF). High-altitude hypobaric hypoxia may exacerbate pulmonary endothelial injury and delay tissue repair, but its impact on the severity and reversibility of ALF-related pancreatitis and ARDS remain uncharacterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      A 44-year-old male (Body mass index 31.7 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) presented with jaundice, oliguria and progressive hypoxemic respiratory failure 1 month after rapid ascent from 1,190 m to 3,650 m. He was diagnosed with HEV-associated ALF, severe refractory ARDS, stage 3 acute kidney injury (AKI) and concurrent severe acute pancreatitis. Despite lung-protective ventilation, neuromuscular blockade and daily prone positioning, hypoxemia remained refractory at high altitude. The patient also received continuous renal replacement therapy and artificial liver support with dual plasma molecular adsorption system plus double filtration plasmapheresis. After 17 days, his condition stabilized but ARDS and AKI recovery was delayed. Following transfer to a hospital at 500\u00a0m altitude, oxygenation, liver and kidney function improved significantly within 3 weeks.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Sustained high-altitude hypoxia may contribute to refractoriness and delayed recovery of ALF-related ARDS. Altitude descent may be a valuable adjuvant strategy for hemodynamically stable patients with refractory hypoxemia, pending further prospective validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2026.1947307","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T04:31:44Z","timestamp":1789533104000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Acute liver failure induced by hepatitis E virus complicated with pancreatitis and refractory acute respiratory distress syndrome after rapid ascent to high altitude: a case report and literature review"],"prefix":"10.3389","volume":"17","author":[{"given":"Bowen","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Emergency, General Hospital of Xizang Military Command","place":["Lhasa, Tibet, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjia","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Emergency, General Hospital of Xizang Military Command","place":["Lhasa, Tibet, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Intensive Care Center, General Hospital of Xizang Military Command","place":["Lhasa, Tibet, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Liu","sequence":"additional","affiliation":[{"name":"Intensive Care Center, General Hospital of Xizang Military Command","place":["Lhasa, Tibet, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youjian","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Emergency, General Hospital of Xizang Military Command","place":["Lhasa, Tibet, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Emergency, General Hospital of Xizang Military Command","place":["Lhasa, Tibet, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliang","family":"Wang","sequence":"additional","affiliation":[{"name":"Intensive Care Center, General Hospital of Xizang Military Command","place":["Lhasa, Tibet, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1136\/gutjnl-2012-302779","article-title":"Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus","volume":"62","author":"Banks","year":"2013","journal-title":"Gut"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/ehjopen\/oeaf017","article-title":"Pulmonary haemodynamics by echocardiography over 3 days of acclimatization in lowlanders with chronic obstructive pulmonary disease travelling to 3100\u2005m of high altitude","volume":"5","author":"Bitos","year":"2025","journal-title":"Eur. Heart J. Open"},{"key":"B3","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41392-025-02531-1","article-title":"Altitude hypoxia and hypoxemia: pathogenesis and management","volume":"11","author":"Cai","year":"2026","journal-title":"Signal Transduction Targeted Ther."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.12890\/2024_004378","article-title":"An acute infection due to hepatitis E in the context of a patient with rituximab and methotrexate therapy","volume":"11","author":"Cordero P\u00e9rez","year":"2024","journal-title":"Eur. J. Case Rep. Intern. Med."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/liv.70727","article-title":"Acute HEV infection is a relevant cause of decompensation and ACLF in patients with liver cirrhosis","volume":"46","author":"Dinkelborg","year":"2026","journal-title":"Liver Int. Off. J. Int. Assoc. For. Study Liver"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms11122898","article-title":"High incidence of acute liver failure among patients in Egypt coinfected with hepatitis A and hepatitis E viruses","volume":"11","author":"El-Mokhtar","year":"2023","journal-title":"Microorganisms"},{"key":"B7","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1186\/s12985-021-01714-w","article-title":"Hepatitis E virus infection in a patient with alcohol related chronic liver disease: a case report of acute-on-chronic liver failure","volume":"18","author":"Fantilli","year":"2021","journal-title":"Virol. J."},{"key":"B8","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/s41572-024-00526-w","article-title":"Altitude illnesses","volume":"10","author":"Gatterer","year":"2024","journal-title":"Nat. Rev. Dis. Primers"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1965","DOI":"10.1111\/liv.13861","article-title":"Acute liver failure caused by hepatitis E virus genotype 3 and 4: a systematic review and pooled analysis","volume":"38","author":"Haffar","year":"2018","journal-title":"Liver Int."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2026.106461","article-title":"Neutralizing antibodies as a therapy for hepatitis E virus: advances, challenges and opportunities","volume":"252","author":"Howell","year":"2026","journal-title":"Antiviral Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2477","DOI":"10.5812\/kowsar.1735143x.3757","article-title":"Hepatitis E","volume":"379","author":"Kamar","year":"2012","journal-title":"Lancet"},{"key":"B12","doi-asserted-by":"publisher","first-page":"17086","DOI":"10.1097\/mog.0b013e32835ff238","article-title":"Hepatitis E virus infection","volume":"3","author":"Kamar","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"B13","doi-asserted-by":"publisher","first-page":"22","DOI":"10.3892\/mi.2024.146","article-title":"Severe hepatitis E virus genotype 3b in a patient with alcohol-associated liver disease: a case report","volume":"4","author":"Kanda","year":"2024","journal-title":"Med. Int. (Lond)"},{"key":"B14","doi-asserted-by":"publisher","first-page":"c179","DOI":"10.1159\/000339789","article-title":"KDIGO clinical practice guidelines for acute kidney injury","volume":"120","author":"Khwaja","year":"2012","journal-title":"Nephron. Clin. Pract."},{"key":"B15","doi-asserted-by":"publisher","first-page":"136","DOI":"10.3855\/jidc.18341","article-title":"Clinical and virological profile of locally acquired acute hepatitis E in South Bulgaria","volume":"18","author":"Komitova","year":"2024","journal-title":"J. Infect. Dev. Ctries"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.aohep.2025.102165","article-title":"Pancreatic involvement and its prognostic impact in acute-on-chronic liver failure","volume":"31","author":"Kramer","year":"2026","journal-title":"Ann. Hepatol."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.idcr.2024.e02069","article-title":"Successful recovery from acute-on-chronic liver failure due to acute hepatitis E virus superinfection in chronic hepatitis B: a case report","volume":"37","author":"Li","year":"2024","journal-title":"IDCases"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/antiox14070835","article-title":"AZU1 as a DNA methylation-driven gene: promoting oxidative stress in high-altitude pulmonary edema","volume":"14","author":"Li","year":"2025","journal-title":"Antioxidants (Basel Switzerland)"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2024.116471","article-title":"Hepatitis E virus and SARS-CoV-2 co-infection in an immunocompromised patient: a case report","volume":"110","author":"Liu","year":"2024","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3390\/tropicalmed11030082","article-title":"Global temporal trends and projections of acute hepatitis E epidemiology for adults 65 years and older from 1990 to 2021: Global burden of disease 2021 based study","volume":"11","author":"Ma","year":"2026","journal-title":"Trop. Med. Infect. Dis."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.73260","article-title":"Acute viral hepatitis E presenting with Bell's palsy and acute pancreatitis: a case report","volume":"16","author":"Malakar","year":"2024","journal-title":"Cureus"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.56344","article-title":"Acute hepatitis E virus infection triggering autoimmune hepatitis in a patient with chronic liver disease: case report and the review of the literature","volume":"16","author":"Malakar","year":"2024","journal-title":"Cureus"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.38101","article-title":"Fulminant hepatitis A and E co-infection leading to acute liver failure: a case report","volume":"15","author":"Malik","year":"2023","journal-title":"Cureus"},{"key":"B24","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1164\/ajrccm-conference.2023.207.1_meetingabstracts.a6229","article-title":"A new global definition of acute respiratory distress syndrome","volume":"209","author":"Matthay","year":"2024","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1089\/ham.2011.1083","article-title":"Liver function in rats acclimatized to a simulated altitude of 5500 m","volume":"14","author":"Ou","year":"2013","journal-title":"High Alt. Med. Biol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e1129","DOI":"10.1093\/infdis\/jiaf134","article-title":"Population-based estimates of hepatitis E virus-associated mortality in Bangladesh","volume":"231","author":"Paul","year":"2025","journal-title":"J. Infect. Dis."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1016\/j.jhep.2016.11.016","article-title":"Hepatitis E virus: infection beyond the liver","volume":"66","author":"Pischke","year":"2017","journal-title":"J. Hepatol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/s41575-025-01159-4","article-title":"Acute-on-chronic liver failure: pathophysiological mechanisms and clinical management","volume":"23","author":"Sarin","year":"2026","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.imj.2026.100259","article-title":"Hepatitis E virus and renal injury: a review of pathogenesis, pathology, and clinical management","volume":"5","author":"Shen","year":"2026","journal-title":"Infect. Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.14309\/ajg.0000000000002340","article-title":"Acute liver failure guidelines","volume":"118","author":"Shingina","year":"2023","journal-title":"Am. J. Gastroenterol."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1177\/15578682261428873","article-title":"High-altitude environment and chronic obstructive pulmonary disease: epidemiology, pathological mechanisms, and clinical management","volume":"27","author":"Wei","year":"2026","journal-title":"High Alt. Med. Biol."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3390\/antiox15010036","article-title":"High-altitude hypoxia injury: systemic mechanisms and intervention strategies on immune and inflammatory responses","volume":"15","author":"Zhang","year":"2025","journal-title":"Antioxidants (Basel Switzerland)"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111847","article-title":"\u03b2-hydroxybutyrate inhibits ferroptosis-mediated pancreatic damage in acute liver failure through the increase of H3K9bhb","volume":"41","author":"Zheng","year":"2022","journal-title":"Cell Rep."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2026.1947307\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T04:31:58Z","timestamp":1789533118000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2026.1947307\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":33,"alternative-id":["10.3389\/fphys.2026.1947307"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2026.1947307","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]},"article-number":"1947307"}}