{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T07:06:02Z","timestamp":1784099162262,"version":"3.55.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) kills about 830,000 people each year, and most cases arise in chronic viral hepatitis. Better risk markers would let clinicians focus surveillance where it matters. Mac-2 binding protein glycosylation isomer (M2BPGi) is a serum glycobiomarker of liver fibrosis. Several cohort studies tie elevated M2BPGi to HCC. No quantitative synthesis has pooled this evidence across viral etiologies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched PubMed\/MEDLINE, Embase, the Cochrane Library, Web of Science, and Scopus through April 2026 for longitudinal studies that reported hazard ratios (HRs) for HCC linked to elevated M2BPGi in chronic hepatitis B (CHB) or C (HCV). We registered the protocol with PROSPERO. The primary pool restricted to longitudinal studies with categorical cutoffs that reported HRs. We used random-effects meta-analysis with restricted maximum likelihood and the Hartung\u2013Knapp adjustment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty-three publications (24 study entries) met inclusion criteria. The primary pool of 15 longitudinal categorical HR-reporting studies covered 12,161 participants and at least 1,189 HCC events. The pooled HR was 4.61 (95% CI 3.24\u20136.54;\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.0001) with low heterogeneity (I\n                      <jats:sup>2<\/jats:sup>\n                      = 25.6%). The 95% prediction interval ran from 2.08 to 10.18. The effect held across etiology (CHB\n                      <jats:italic>k<\/jats:italic>\n                      = 5 HR 4.12; HCV\n                      <jats:italic>k<\/jats:italic>\n                      = 10 HR 5.07; p_subgroup = 0.62) and across measurement timing (baseline HR 3.21; on\/post-treatment HR 5.62; post-SVR HR 5.45; p_subgroup = 0.23). Two sensitivity pools re-introducing OR-based studies gave HR 4.71 (\n                      <jats:italic>k<\/jats:italic>\n                      = 16) and HR 4.89 (\n                      <jats:italic>k<\/jats:italic>\n                      = 17). Egger\u2019s test was positive (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0003); trim-and-fill imputed six studies and pulled the adjusted HR to 3.53.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Elevated serum M2BPGi is strongly and consistently associated with HCC development in patients with chronic hepatitis B and C. The effect holds across etiology, treatment status, and measurement timing\u2013including after sustained virological response. Funnel asymmetry suggests the true effect is closer to a 3.5-fold than a 4.6-fold risk increase, still large enough to matter clinically. M2BPGi is a credible candidate to layer onto current viral hepatitis surveillance, particularly for risk stratification after virological control.<\/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\/CRD420261372566<\/jats:ext-link>\n                      , identifier CRD420261372566.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1897953","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T06:11:22Z","timestamp":1784095882000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum M2BPGi as a predictor of hepatocellular carcinoma development in chronic hepatitis B and C: a systematic review and 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