Personalizing Hepatocellular Carcinoma: The Emerging Era of Precision Management

Dear Colleagues,

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. It ranks as a leading cause of cancer-related mortality worldwide, and its incidence is rising globally. While viral hepatitis (HBV and HCV) remains the predominant etiology of cirrhosis, dysmetabolic liver disease is rapidly becoming the leading cause of chronic liver disease and, consequently, of HCC. Patients with metabolic-associated steatotic liver disease (MASLD) present specific challenges for hepatologists, due to both the difficulty in applying effective treatments and the typically low degree of fibrosis presented. Despite significant advancements in prevention and screening programs, particularly for viral hepatitis, we are witnessing shifts in the biological behavior of HCC: diagnoses are increasingly made at late stages and often in patients without advanced fibrosis, a scenario that evades traditional HCC surveillance protocols. We are living in an era in which the most appropriate approach is to personalize every follow‑up and every therapeutic decision, choosing the optimal option case by case. This is precisely what innovation in diagnostics and therapy is moving toward, with early detection and targeted therapies currently hot topics. Liquid biopsy panels, advanced imaging radiomics, and AI‑integrated imaging offer promise to detect sub‑centimeter tumors or pre‑neoplastic clonal expansions missed by conventional surveillance. Regarding therapeutic strategies, in recent years, there has been a paradigm shift toward a more patient-centered approach, moving beyond the traditional reliance on tumor staging, and ICIs are the leading actor in this scenario. This approach has led to encouraging results, including successful outcomes with conversion therapies. Although targeted therapies are still far from playing a crucial role in HCC treatment, they are already yielding encouraging results. This Special Issue will provide a comprehensive overview of current and emerging strategies for prevention, early detection, multidisciplinary management, and treatment innovation. Topics of interest include novel biomarkers, imaging innovations, risk stratification models, and evolving treatment approaches.

Dr. Mario Capasso
Dr. Valentina Cossiga
Dr. Fabrizio Romano
Guest Editors

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• hepatocellular carcinoma (HCC)
• early diagnosis
• cancer prevention
• biomarkers
• liver imaging
• immunotherapy
• systemic treatment
• liver cancer management