REVIEW article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Efficacy and Safety of Tyrosine Kinase Inhibitors in Advanced Hepatocellular Carcinoma Patients with Child-Pugh A and B Cirrhosis: A Meta-Analysis
Provisionally accepted
- Guangxi Medical University Cancer Hospital, Nanning, China
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Background:Hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality. Tyrosine kinase inhibitors (TKIs) are widely used in advanced HCC, yet outcomes may differ by hepatic reserve. We compared the efficacy and safety of guideline-recommended TKIs between patients with Child–Pugh A (CP-A) and Child–Pugh B (CP-B) cirrhosis. Methods: We conducted a PRISMA-guided systematic review and meta-analysis (searches through October 15, 2024). Eligible studies evaluated TKI monotherapy and reported outcomes separately for CP-A and CP-B. Primary endpoints were overall response rate (ORR), disease control rate (DCR), and grade ≥3 treatment-related adverse events (trAEs). Pooled risk ratios (RRs) with 95% CIs were estimated using prespecified random-effects models; small-study effects were explored with funnel plots (and Egger's test when k≥10). Results: Twenty-four studies met inclusion. Pooled analyses showed no significant differences between CP-B and CP-A for ORR (k≈15; RR 1.02, 95% CI 0.83–1.27; I² 42.8%) and DCR (k≈10; RR 0.87, 95% CI 0.58–1.29; I² 83.1%). For grade ≥3 trAEs (k≈9), CP-A had a lower risk than CP-B (CP-A vs CP-B RR 0.79, 95% CI 0.63–1.00; I² 61.7%), indicating a borderline increase in severe toxicity among CP-B. Funnel plots showed no clear asymmetry; Egger's test for ORR was negative (p=0.94), and tests were not performed for DCR and trAEs due to k<10. Conclusions: In advanced HCC treated with TKI monotherapy, radiologic efficacy (ORR, DCR) appears broadly comparable between CP-B and CP-A, whereas CP-B may experience higher rates of grade ≥3 toxicities. TKIs remain a reasonable option for selected CP-B patients, provided dosing is individualized and adverse events are closely monitored. Prospective, stratified studies are needed to refine patient selection and dose management in CP-B.
Keywords: Child–Pugh classification, Hepatocellular Carcinoma, Meta-analysis, Treatment-related adverse events, tyrosine kinase inhibitors
Received: 22 Aug 2025; Accepted: 03 Feb 2026.
Copyright: © 2026 Liu, Li, Li and Xiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Bangde Xiang
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