Sequencing-based biomarker discovery in liver transplantation: a narrative review

Background and Objective: Liver transplantation is a life-saving therapy for patients with end-stage liver disease, with continuing advancements in surgical techniques, organ preservation, and post-transplant management leading to excellent outcomes. Nevertheless, transplantation remains biologically complex and is shaped by the heterogeneity of both donor organs and recipients, as well as dynamic responses to ischemia-reperfusion injury (IRI) and immune-mediated processes. Many of these mechanisms are incompletely captured by conventional clinical parameters, limiting risk stratification and deeper mechanistic insights. Advances in sequencing-based transcriptomics technologies have emerged as powerful tools to resolve cellular and molecular mechanisms underlying graft injury and thereby enable the discovery of novel biomarkers that more accurately reflect graft (dys)function. The aim of this review was to summarize the use of sequencing-based transcriptomics in liver transplantation to date.

Methods: A narrative literature review of original human studies indexed in PubMed/MEDLINE over the past 10 years was performed to evaluate sequencing-based transcriptomics for biomarker discovery across the liver transplantation timeline. This covered organ preservation strategies, including static cold storage and machine perfusion techniques, as well as IRI, graft dysfunction, immune responses and post-transplant complications.

Key Content and Findings: Transcriptomic profiling identifies distinct molecular signatures associated with donor type, preservation modality, and graft viability. Single-cell and spatial transcriptomics further define cell-type-specific immune networks underlying tolerance, rejection, and biliary complications.

Conclusions: Sequencing-based transcriptomics provides mechanistic insights and identifies candidate molecular signatures throughout the transplantation timeline, with the potential to complement standard clinical and laboratory-based assessment methods. Standardization, rapid sequencing workflows, and prospective validation are essential for clinical translation and real-time molecular decision-making in liver transplantation.