Precision medicine in liver transplantation for hepatocellular carcinoma: applications and prospects of third-generation sequencing technology

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Liver transplantation (LT) remains a vital treatment for HCC, yet it still faces numerous challenges in patient selection, recurrence monitoring, and personalized therapy. Third-generation sequencing (TGS), with its advantages of long read length, high throughput, direct detection of epigenetic modifications, real-time analysis and high accuracy, offers promise for advancing precision medicine in LT. While previous reviews have focused on TGS technical features, this review uniquely synthesizes its role in addressing specific clinical challenges in LT-HCC management and critically assesses its translational pathway. Specifically, it systematically examines TGS applications in candidate screening, recurrence monitoring, and personalized therapy for LT-HCC, analyzes its prospects for clinical translation, and aims to provide new insights for precise HCC treatment. We also discuss barriers to implementation and suggest solutions for integrating TGS into clinical workflows. This review provides a roadmap for leveraging TGS to revolutionize precision medicine in transplant hepatology.