{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T06:29:55Z","timestamp":1773815395619,"version":"3.50.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"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. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This meta-analysis aimed to evaluate the influence of vitamin K (VK) as an adjunctive therapy on the prognosis of patients with hepatocellular carcinoma (HCC), with a specific focus on its clinical value in non-resected individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically retrieved Chinese and English databases, including PubMed and Embase, to select randomized controlled trials (RCTs) and cohort studies comparing VK combined with standard therapy versus standard therapy alone. Methodological quality was evaluated via the Newcastle-Ottawa Scale for cohort studies and the Cochrane Risk of Bias tool (RoB-2) for RCTs. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoint was recurrence risk. Pooled hazard ratios (HRs) and relative risks (RRs) were computed by fixed- or random-effects models. Subgroup analyses (surgery vs. transarterial chemoembolization [TACE]) and time stratification (12\u201348M) were conducted to explore heterogeneity sources.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eleven studies involving 688 subjects were incorporated. The fixed-effects meta-analysis indicated that VK combined with standard therapy did not significantly improve OS (pooled HR = 0.77, 95% CI: 0.58\u20131.01). However, this combination prolonged PFS (pooled HR = 0.62, 95% CI: 0.47\u20130.82). Subgroup analysis based on PFS demonstrated more pronounced benefit in TACE-treated subjects (HR = 0.51, 95% CI: 0.34\u20130.77). Furthermore, VK combined with standard therapy reduced recurrence risk (pooled HR = 0.26, 95% CI: 0.15\u20130.46).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Adjunctive VK improves PFS and reduces recurrence risk in HCC subjects, demonstrating particular benefit for those with unresectable tumors receiving TACE. No significant OS advantage was observed. Future investigations should optimize VK dosing and administration strategies and explore its potential synergy with immunotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251106693<\/jats:ext-link>\n                      , identifier CRD420251106693.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1765445","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T05:36:42Z","timestamp":1773812202000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The role of vitamin K in the prognosis of patients with hepatocellular carcinoma: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Lang","family":"Guo","sequence":"first","affiliation":[{"name":"Wuming Hospital Affiliated to Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaqiong","family":"Wang","sequence":"additional","affiliation":[{"name":"Graduate Institute, Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenkun","family":"Tan","sequence":"additional","affiliation":[{"name":"Graduate Institute, Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingli","family":"Lu","sequence":"additional","affiliation":[{"name":"Graduate Institute, Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zha","family":"Peng","sequence":"additional","affiliation":[{"name":"Dongguan Hospital of Guangzhou University of Traditional Chinese Medicine","place":["Dongguan, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai","family":"Huang","sequence":"additional","affiliation":[{"name":"Wuming Hospital Affiliated to Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s13045-020-01029-3","article-title":"STOML2 potentiates metastasis of hepatocellular carcinoma by promoting PINK1-mediated mitophagy and regulates sensitivity to lenvatinib","volume":"14","author":"Zheng","year":"2021","journal-title":"J Hematol Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-023-10084-4","article-title":"Hepatocellular carcinoma: molecular mechanism, targeted therapy, and biomarkers","volume":"42","author":"Wang","year":"2023","journal-title":"Cancer Metastasis Rev"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000466","article-title":"AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma","volume":"78","author":"Singal","year":"2023","journal-title":"Hepatology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s13046-024-02957-5","article-title":"EGR1 suppresses HCC growth and aerobic glycolysis by transcriptionally downregulating PFKL","volume":"43","author":"Pan","year":"2024","journal-title":"J Exp Clin Cancer Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.02.032","article-title":"TREM2(+) macrophages suppress CD8(+) T-cell infiltration after transarterial chemoembolisation in hepatocellular carcinoma","volume":"79","author":"Tan","year":"2023","journal-title":"J Hepatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s40620-019-00685-0","article-title":"Vitamin K effects in human health: new insights beyond bone and cardiovascular health","volume":"33","author":"Fusaro","year":"2020","journal-title":"J Nephrol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.6118\/jmm.24023","article-title":"Vitamin K: calcium metabolism modulator for menopausal women","volume":"30","author":"Kim","year":"2024","journal-title":"J Menopausal Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v3.i9.757","article-title":"Vitamin K and hepatocellular carcinoma: The basic and clinic","volume":"3","author":"Jinghe","year":"2015","journal-title":"World J Clin Cases"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/nu14204219","article-title":"Vitamin K contribution to DNA damage-advantage or disadvantage? 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