Author information

• ¹Department of Pathology and Pittsburgh Liver Institute, University of Pittsburgh, School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
• ²Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Staford, CA, 94303, USA.
• ³Department of Pathology and Pittsburgh Liver Institute, University of Pittsburgh, School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Electronic address: smonga@pitt.edu.
• ⁴Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Staford, CA, 94303, USA. Electronic address: dhanaser@stanford.edu.

Abstract

Hepatocellular carcinoma (HCC) diagnosis and management have undergone significant improvements in recent years. With the introduction of immunotherapy-based combination therapy, there has been a notable expansion in treatment options for patients with unresectable HCC. Simultaneously, innovative molecular tests for early detection and management of HCC are emerging. This progress prompts a key question: as liquid biopsy techniques rise in prominence, will they replace traditional tissue biopsies, or will both techniques remain relevant? Given the ongoing challenges of early HCC detection, including issues with ultrasound sensitivity, accessibility, and patient adherence to surveillance, the evolution of diagnostic techniques is more relevant than ever. Furthermore, the accurate stratification of HCC is limited by the absence of reliable biomarkers which can predict response to therapies. While the advantages of molecular diagnostics are evident, their potential has not yet been fully harnessed, largely because tissue biopsies are not routinely performed for HCC. Liquid biopsies, analyzing components such as circulating tumor cells, DNA, and extracellular vesicles, provide a promising alternative, though they still face challenges in sensitivity, cost, and accessibility. The early results from multianalyte liquid biopsy panels are promising and suggest they could play a transformative role in HCC detection and management, however, comprehensive clinical validation is still ongoing. In this review, we explore the challenges and potential of both tissue and liquid biopsy, highlighting that these diagnostic methods, while distinct in their approaches, are set to jointly reshape the future of HCC management.