Circulating tumour DNA for a minimal residual disease assessment and recurrence risk in hepatocellular carcinoma: a systematic review and meta-analysis.

Hepatocellular carcinoma (HCC) relapse remains high after curative-intent treatment due to occult minimal residual disease. Circulating tumour DNA (ctDNA) has emerged as a noninvasive biomarker. Systematic search of MEDLINE, EMBASE and the Cochrane Library up to November 2024 identified studies evaluating plasma ctDNA in non-metastatic HCC patients undergoing curative-intent treatment. Hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence-free survival (RFS) and overall survival (OS) were pooled using random-effects models; sensitivity and specificity for predicting recurrence were summarised. Ten retrospective studies (n = 793) met inclusion criteria. Postoperative ctDNA positivity was associated with shorter RFS (HR 4.48; 95% CI 2.56-7.82; I² = 78%; p < 0.001) and worse OS (HR 2.99; 95% CI 1.94-4.61; I² = 47%; p < 0.001). Baseline ctDNA detection predicted reduced RFS (HR 3.54; 95% CI 1.97-6.38; I² = 35%; p < 0.001). Sensitivity ranged 33-82% and specificity 41-100%, reflecting methodological heterogeneity. Leave-one-out analyses confirmed robustness. Plasma ctDNA is a potent prognostic marker of recurrence and survival in non-metastatic HCC. Prospective trials incorporating ctDNA could optimise postoperative surveillance and guide adjuvant therapy selection.