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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.<\/jats:p>","DOI":"10.3389\/fphar.2026.1871275","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:47:21Z","timestamp":1788781641000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["From mechanisms to practice: risk management and multidisciplinary decision-making for systemic treatment-related liver injury in HBV-associated hepatocellular carcinoma"],"prefix":"10.3389","volume":"17","author":[{"given":"Yachao","family":"Tao","sequence":"first","affiliation":[{"name":"Center of Infectious Diseases, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghong","family":"Wang","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Mao","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuezhong","family":"Lei","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enqiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1056\/NEJMoa1717002","article-title":"Cabozantinib in patients with advanced and progressing hepatocellular carcinoma","volume":"379","author":"Abou-Alfa","year":"2018","journal-title":"N. 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