Liquid Biopsy in Hepatocellular Carcinoma: ctDNA as a Potential Biomarker for Diagnosis and Prognosis.

purpose of reviewHepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with rising incidence and mortality. Early-stage HCC is often asymptomatic, and the lack of reliable early diagnostic markers leads to late-stage diagnosis with limited treatment options. Current treatment relies on tumour staging and patient status, but accurate staging requires invasive procedures that fail to capture tumour heterogeneity and progression. There is an urgent need for less invasive diagnostic strategies, such as liquid biopsy technologies, which allow for repeated sampling and real-time analysis of tumour dynamics. Liquid biopsies, including circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA), offer the potential to monitor recurrence, metastasis, and treatment responses, potentially transforming HCC clinical management by enabling earlier intervention and personalised treatment strategies. RECENT

findingsRecent studies emphasise the potential of ctDNA as a non-invasive biomarker by targeting DNA methylation for early HCC detection, enabling timely intervention and personalised treatment to improve patient outcomes. Comparative analyses have shown that ctDNA mutation testing outperforms alpha-fetoprotein (AFP), with a sensitivity of 85% and a specificity of 92%, compared to 60% sensitivity and 80% specificity for AFP. Additionally, profiling the ctDNA mutation landscape of 100 HCC patients has identified recurrent mutations in genes such as TP53, CTNNB1, and AXIN1. ctDNA appears to be a promising non-invasive biomarker in the clinical management of HCC patients, with the sensitivity and specificity improving by 41.67% and 15% respectively. The ctDNA mutations, particularly those targeting DNA methylation, highlight great potential for precision medicine, critical for early diagnosis and prognosis of HCC.