ArticleTranslational cancer research2026
Hepatotoxicity of immune checkpoint inhibitor plus targeted therapy versus tyrosine kinase inhibitor monotherapy in unresectable hepatocellular carcinoma: a systematic review and meta-analysis.
Article in Translational cancer research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 authors.
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Abstract
Background: Immune checkpoint inhibitor (ICI) plus targeted therapy has revolutionized the treatment paradigm for unresectable hepatocellular carcinoma (HCC). However, evidence regarding liver toxicity associated with ICI plus targeted therapy remains limited, particularly with respect to fatal adverse events (FAEs) and serious adverse events (SAEs). Therefore, this meta-analysis aimed to systematically compare the hepatotoxicity profiles between ICI plus targeted therapy and tyrosine kinase inhibitor (TKI) monotherapy in patients with unresectable HCC. Methods: We systematically searched the Cochrane Library, Embase, and PubMed databases from inception through March 2026 for randomized controlled trials (RCTs) enrolling patients with unresectable HCC treated with ICI-targeted therapy or TKI monotherapy. Outcomes included hepatotoxicity-related SAEs, FAEs, and liver function markers: total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), ascites, conjugated bilirubin, abnormal liver function, alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT). Pooled analyses were performed using a random-effects model. Results: Eight RCTs encompassing 4,379 patients were included. Compared with TKI monotherapy, ICI plus targeted therapy was associated with a significantly higher risk of hepatotoxicity-related SAEs [odds ratio (OR), 1.71; 95% confidence interval (CI), 1.11-2.63; P=0.02; I Conclusions: ICI plus targeted therapy was more likely to cause an increase in hepatotoxicity, especially elevated bilirubin levels. These findings warrant close clinical monitoring.
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