{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T21:38:17Z","timestamp":1768772297043,"version":"3.49.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Lipoprotein Z (LP\u2010Z) is an abnormal free cholesterol (FC)\u2013enriched LDL\u2010like particle discovered from patients with cholestatic liver disease. This study aims to define the diagnostic value of LP\u2010Z in alcohol\u2010associated hepatitis (AH) and interrogate the biology behind its formation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>We measured serum levels of LP\u2010Z using nuclear magnetic resonance spectroscopy, a well\u2010established clinical assay. Serum levels of LP\u2010Z were significantly elevated in four AH cohorts compared with control groups, including heavy drinkers and patients with cirrhosis. We defined a Z\u2010index, calculated by the ratio of LP\u2010Z to total apolipoprotein B\u2013containing lipoproteins, representing the degree of deviation from normal VLDL metabolism. A high Z\u2010index was associated with 90\u2010day mortality independent from the Model for End\u2010Stage Liver Disease (MELD) and provided added prognosticative value. Both a Z\u2010index \u2264 0.6 and a decline of Z\u2010index by \u22650.1 in 2 weeks predicted 90\u2010day survival. RNA\u2010sequencing analyses of liver tissues demonstrated an inverse association in the expression of enzymes responsible for the extrahepatic conversion of VLDL to LDL and AH disease severity, which was further confirmed by the measurement of serum enzyme activity. To evaluate whether the FC in LP\u2010Z could contribute to the pathogenesis of AH, we found significantly altered FC levels in liver explant of patients with AH. Furthermore, FC in reconstituted LP\u2010Z particles caused direct toxicity to human hepatocytes in a concentration\u2010dependent manner, supporting a pathogenic role of FC in LP\u2010Z.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Impaired lipoprotein metabolism in AH leads to the accumulation of LP\u2010Z in the circulation, which is hepatotoxic from excessive FC. A Z\u2010index \u2264 0.6 predicts 90\u2010day survival independent from conventional biomarkers for disease prognostication.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32203","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T04:40:16Z","timestamp":1634791216000},"page":"968-982","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":6,"title":["Lipoprotein Z, a hepatotoxic lipoprotein, predicts outcome in alcohol\u2010associated hepatitis"],"prefix":"10.1097","volume":"75","author":[{"given":"Kunpeng","family":"Hu","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Department of Medicine,Beth Israel Deaconess Medical Center,Harvard Medical School,Boston,Massachusetts,USA"},{"name":"Division of General Surgery,The Third Affiliated Hospital of Sun Yat\u2010Sen University,Guangzhou,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria C.","family":"Perez\u2010Matos","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Department of Medicine,Beth Israel Deaconess Medical Center,Harvard Medical School,Boston,Massachusetts,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josepmaria","family":"Argemi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,University of Pittsburgh Medical Center,Pittsburgh,Pennsylvania,USA"},{"name":"Hepatology Program,Centro de Investigacion Medica Aplicada, Liver Unit,Clinica Universidad de Navarra,Instituto de Investigacion de Navarra,University of Navarra,Pamplona,Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Vilar\u2010Gomez","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Indiana 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