SYSTEMATIC REVIEW article
Front. Pharmacol.
Sec. Gastrointestinal and Hepatic Pharmacology
A Network Meta-analysis of First-line Treatment Options for Patients with Child-Pugh Class B Functional Hepatocellular Carcinoma: Comparison of Efficacy and Safety
Provisionally accepted
Yu-Xuan Zhang1,2
Junyi Wu2
Jia-Yi Wu2
Zhen-Xin Zeng1,2Rong-Jian Pan1,2Xiang-Ye Ou1,2
Yi-Nan Li1,2
Maolin Yan1,2*- 1Shengli Clinical Medical College, Fujian Medical University, Fuzhou, China
- 2Fuzhou University Affiliated Provincial Hospital, Fuzhou, China
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Introduction: Management of patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh class B liver function is challenging owing to compromised hepatic functional reserve, affecting treatment selection and outcomes, as many systemic therapies demonstrate altered pharmacokinetics and increased toxicity in this population. Current treatment guidelines predominantly focus on patients with preserved liver function (Child-Pugh A), creating a critical evidence gap for the optimal management of patients with Child-Pugh B liver function. This network meta-analysis (NMA) evaluated first-line therapies for patients with advanced HCC and Child-Pugh B cirrhosis, addressing current evidence gaps to guide optimal treatment selection for this high-risk population. Methods: The PubMed, Embase, and Cochrane Library databases were searched until October 31, 2024. Randomized controlled trials and prospective cohort studies were included if they involved patients with advanced HCC and Child-Pugh class B liver function, evaluated first-line therapeutic agents, and reported overall survival (OS) and/or progression-free survival (PFS) with 95% confidence intervals. Bayesian NMA was employed to evaluate treatment efficacy and safety. Results: Eleven studies comprising 2,536 patients were included in the NMA. Lenvatinib exhibited the greatest probability of ideal efficacy for OS, while atezolizumab and bevacizumab combination therapy demonstrated the highest likelihood of optimal performance in terms of PFS. The overall incidence of adverse events (AEs) was 68.58%. The predominant grade 3–4 AEs included hypertension, proteinuria, hand-foot syndrome, and abnormal liver function. Conclusion: Atezolizumab and bevacizumab combination therapy demonstrated the optimal net benefit regarding PFS and reduced toxicity, whereas lenvatinib monotherapy exhibited the greatest net benefit in OS but with increased toxicity.
Keywords: Hepatocellular Carcinoma, Child-Pugh class B, Network meta-analysis, first-linetreatment, efficacy, Safety
Received: 15 Sep 2025; Accepted: 26 Nov 2025.
Copyright: © 2025 Zhang, Wu, Wu, Zeng, Pan, Ou, Li and Yan. 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: Maolin Yan
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