{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T04:56:16Z","timestamp":1790571376337,"version":"4.1.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"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. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>CT-derived skeletal muscle index (SMI) and skeletal muscle density (SMD) may complement nutritional and functional assessment before liver transplantation, but pathways linking these body-composition phenotypes to long-term outcomes remain unclear. We evaluated whether cumulative 90-day postoperative complication burden was compatible with an intermediate pathway between lower preoperative SMI or SMD and long-term mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single-center retrospective cohort used a postoperative day-90 landmark, restricting the primary analysis to recipients alive and under follow-up at day 90. SMI and SMD were analyzed separately, with the 90-day Comprehensive Complication Index (CCI) as the mediator and all-cause mortality during a prespecified 5-year post-landmark window as the outcome. Linear mediator and Cox outcome models adjusted for hepatocellular carcinoma, Eastern Cooperative Oncology Group performance status, and MELD 3.0. Percentile 95% confidence intervals (CIs) were obtained from 1,000 nonparametric bootstrap resamples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 245 recipients screened, 205 entered the landmark cohort; 56 (27.3%) died during the prespecified 5-year post-landmark analysis window. Median analyzed follow-up was 3.33\u202fyears. For a 1-standard deviation decrease, the approximate natural indirect-effect hazard ratios (HRs) through CCI were 1.155 (95% bootstrap CI, 1.033\u20131.326) for SMI and 1.190 (1.062\u20131.382) for SMD. Natural direct-effect CIs included 1 for both exposures, whereas the total-effect CI excluded 1 for SMI but not SMD. Indirect-effect estimates were similar after replacing ECOG with age and delaying outcome follow-up to day 120, but were attenuated after CCI dichotomization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Lower preoperative SMI and SMD showed model-based approximate indirect effects through cumulative postoperative complication burden. These CT-derived muscle phenotypes may complement, but should not replace, comprehensive nutritional and functional assessment. The observational design and incompletely verifiable identification assumptions preclude strict causal or interventional interpretation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1978429","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T04:29:02Z","timestamp":1790569742000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Preoperative CT-derived skeletal muscle phenotypes, postoperative complication burden, and long-term survival after liver transplantation: a 90-day landmark mediation analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Rui","family":"Yu","sequence":"first","affiliation":[{"name":"Fuzong Clinical Medical College of Fujian Medical University","place":["Fuzhou, Fujian, China"]},{"name":"Department of Hepatobiliary and Pancreatic Surgery, 900th Hospital of PLA Joint Logistic Support Force","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Sun","sequence":"additional","affiliation":[{"name":"Fuzong Clinical Medical College of Fujian Medical University","place":["Fuzhou, Fujian, China"]},{"name":"Department of Hepatobiliary and Pancreatic Surgery, 900th Hospital of PLA Joint Logistic Support Force","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Du","sequence":"additional","affiliation":[{"name":"Fuzong Clinical Medical College of Fujian Medical University","place":["Fuzhou, Fujian, China"]},{"name":"Department of Hepatobiliary and Pancreatic Surgery, 900th Hospital of PLA Joint Logistic Support Force","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhi","family":"Lv","sequence":"additional","affiliation":[{"name":"Fuzong Clinical Medical College of Fujian Medical University","place":["Fuzhou, Fujian, China"]},{"name":"Department of Hepatobiliary and Pancreatic Surgery, 900th Hospital of PLA Joint Logistic Support Force","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1111\/ajt.15392","article-title":"Frailty in liver transplantation: an expert opinion statement from the American Society of Transplantation liver and intestinal Community of Practice","volume":"19","author":"Lai","year":"2019","journal-title":"Am J Transplant"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1002\/lt.25792","article-title":"Liver transplant survivorship","volume":"26","author":"Lai","year":"2020","journal-title":"Liver Transpl"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1016\/j.jhep.2016.07.040","article-title":"Sarcopenia from mechanism to diagnosis and treatment in liver disease","volume":"65","author":"Dasarathy","year":"2016","journal-title":"J Hepatol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1007\/s00535-019-01605-6","article-title":"Sarcopenia in cirrhosis: from pathogenesis to interventions","volume":"54","author":"Ebadi","year":"2019","journal-title":"J Gastroenterol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1111\/ajt.15577","article-title":"Myosteatosis to predict inferior perioperative outcome in patients undergoing orthotopic liver transplantation","volume":"20","author":"Czigany","year":"2020","journal-title":"Am J Transplant"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.clnu.2018.08.002","article-title":"GLIM criteria for the diagnosis of malnutrition: a consensus report from the global clinical nutrition community","volume":"38","author":"Cederholm","year":"2019","journal-title":"Clin 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ethical principles for medical research involving human participants","volume":"333","year":"2025","journal-title":"JAMA"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1097\/TP.0000000000002540","article-title":"The declaration of Istanbul on organ trafficking and transplant tourism (2018 edition)","volume":"103","year":"2019","journal-title":"Transplantation"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1097\/TP.0b013e3182985491","article-title":"The national program for deceased organ donation in China","volume":"96","author":"Huang","year":"2013","journal-title":"Transplantation"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1136\/bmj.332.7549.1080","article-title":"The cost of dichotomising continuous 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