From mechanisms to practice: risk management and multidisciplinary decision-making for systemic treatment-related liver injury in HBV-associated hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death globally, with chronic hepatitis B virus (HBV) infection as the predominant risk factor. Systemic therapies including tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), and ICI-antiangiogenic combinations have revolutionized advanced HCC treatment. However, treatment-induced liver injury is a major concern, especially in HBV-related HCC patients with pre-existing inflammation, fibrosis, and cirrhosis, which raises risks of treatment interruption, impaired efficacy, and acute liver failure. Liver injury arises from direct cytotoxicity, immune-mediated hepatitis, vascular damage, and HBV reactivation. This review summarizes the pathophysiological mechanisms of treatment-related liver injury in HBV-related HCC, analyzes the hepatotoxic profiles of tyrosine kinase inhibitors, immune checkpoint inhibitors, combination regimens and emerging agents, and proposes a structured clinical management framework including pretreatment risk assessment, prophylaxis, monitoring, differential diagnosis and severity-based interventions supported by multidisciplinary care. It aims to offer evidence-based guidance for clinicians to preserve liver function while safely administering effective antitumor therapy. The review also highlights key knowledge gaps and future research directions, including predictive biomarkers, personalized risk stratification and proactive safety evaluation of new drugs.