{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:16:10Z","timestamp":1788308170216,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Acute\u2010on\u2010chronic liver failure (ACLF), particularly hepatitis B virus\u2010related ACLF (HBV\u2010ACLF), is a severe condition with high short\u2010term mortality. This study aimed to evaluate the prognostic value of circulating cell\u2010free mitochondrial DNA (cf\u2010mtDNA) in predicting short\u2010term mortality in HBV\u2010ACLF patients. A total of 320 HBV\u2010ACLF patients were included in the study population, with 192 patients in the derivation cohort and 128 in the validation cohort. Plasma cf\u2010mtDNA levels were quantified using qPCR. Plasma cf\u2010mtDNA levels were significantly elevated in HBV\u2010ACLF patients (3.95 log\n                    <jats:sub>10<\/jats:sub>\n                    copies\/\u03bcL) compared to healthy controls (2.99 log\n                    <jats:sub>10<\/jats:sub>\n                    copies\/\u03bcL) and patients with chronic liver disease (3.03 log\n                    <jats:sub>10<\/jats:sub>\n                    copies\/\u03bcL) (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Plasma cf\u2010mtDNA levels progressively increased with disease severity and were associated with multi\u2010organ failure. Sequential measurements of cf\u2010mtDNA showed a significant decrease in survivors (4.00 vs. 3.78 log\n                    <jats:sub>10<\/jats:sub>\n                    copies\/\u03bcL,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.019), while non\u2010survivors maintained persistently elevated levels with minimal change (4.19 vs. 4.15 log\n                    <jats:sub>10<\/jats:sub>\n                    copies\/\u03bcL,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.359). The cut\u2010off value of 3.9 log\n                    <jats:sub>10<\/jats:sub>\n                    copies\/\u03bcL for cf\u2010mtDNA effectively stratified patients into high\u2010 and low\u2010risk groups, with significantly lower survival rates in the high\u2010risk group (28\u2010day: 46.2% vs. 86.0%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001; 90\u2010day: 37.7% vs. 72.1%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Using cf\u2010mtDNA in combination with key clinical parameters, we developed a novel prognostic score that exhibited superior predictive accuracy for 28\u2010 and 90\u2010day mortality (AUROCs: 0.907 and 0.906, respectively), outperforming established prognostic scores (all\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). These findings were validated in an independent cohort. Cf\u2010mtDNA is a superior biomarker for predicting short\u2010term mortality in HBV\u2010ACLF. Its association with multi\u2010organ failure and disease severity highlights the potential utility in early risk assessment and treatment optimization.\n                  <\/jats:p>","DOI":"10.1002\/jmv.70551","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T11:25:21Z","timestamp":1755516321000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Circulating Cell\u2010Free Mitochondrial DNA as a Prognostic Biomarker in Patients With HBV\u2010Related Acute\u2010on\u2010Chronic Liver Failure"],"prefix":"10.1002","volume":"97","author":[{"given":"Qiankun","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Liver Diseases, Shanghai Public Health Clinical Center Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Shanghai Public Health Clinical Center Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Liver Diseases, Shanghai Public Health Clinical Center Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenlu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Liver Diseases, Shanghai Public Health Clinical Center Fudan University Shanghai 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