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 15 October 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; I 2 42.8%) and DCR (k ≈ 10; RR 0.87, 95% CI 0.58–1.29; I 2 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; I 2 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. Conclusion 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.
Liu et al. (2026) studied this question.