Prognostic and diagnostic biomarkers in liver transplantation: A systematic review and meta-analysis.
Camera, A., et al.Liver Transpl. 2025 Dec 1;31(12):1499-1510.
Aims
The authors aim to systematically evaluate prognostic and diagnostic biomarkers after liver transplantation (LT), quantify their association with graft-related outcomes and mortality, and identify combinations with improved prognostic performance.
Interventions
To assess early (≤15 days post-LT) vs late (>15 days) biomarker windows and their association with graft and patient outcomes
Participants
Adult LT recipients across 29 eligible studies: 21 prognostic and 8 diagnostics, pooling 34,922 patients for prognostic analyses and 673 for diagnostic summaries. Studies involving paediatric, split and multi-organ transplantation were excluded.
Outcomes
Primary outcomes assessed for association: EAD, PNF, mortality and composite endpoints (graft failure or mortality; retransplantation or mortality).
Follow-up
Varied across included studies
CET Conclusions
The authors have conducted a rigorous PRISMA-registered meta-analysis from 29 studies totalling 34,922 recipients. Early single biomarkers (pooled HR/OR 0.95 [0.94–0.97) relate to graft-related dysfunction but do not reliably predict mortality across studies. Factor V and creatinine linked to EAD and lactate linked to initial poor graft function. Mortality prediction by single early biomarkers was inconsistent overall but there was significance for ALT, AST and factor V in some studies. Simple early combinations (ALT+AST; GGT/bilirubin) better predict composite failure/mortality than the single markers alone, as is known with the popularity of composites scores such as MEAF, which predicted primary non-function in derivation/validation cohorts. Factor V-based panels (with ALT or IGF-1) have promising stratification power in individualised patient data reconstructions. Late biomarkers showed limited, heterogeneous associations, but creatinine excretion rate, elastography grade, and NAFLD-type panels associated with mortality. I one of the studies APRI, FIB-4, and haemoglobin associated with composite outcomes. Nevertheless, heterogeneity, confounding, and measurement variability reduce overall certainty in any of the biomarker findings. Over half of prognostic studies had moderate to high bias in confounding and measurement domains, and between-study heterogeneity was frequently high. Clinically, their study has strengthened a few readily available panels (MEAF, ALT+AST, GGT/bilirubin etc.) that can support early risk stratification after transplant, while factor V-anchored combinations merit prospective validation before routine adoption. Given the reality of MELD-3.0 organ allocation and increasing non-conventional donors, centres could reasonably pilot factor-V–based panels, but more universal adoption should await a multicentre prospective study.
Trial registration
PROSPERO - CRD42023387074