The Prognostic Value of CRP/Alb Ratio in Predicting Overall Survival for Hepatocellular Carcinoma Treated with Transcatheter Intra-Arterial Therapy Combined with Molecular-Targeted Agents and PD-1/PD-L1 Inhibitors

Overview

Journal J Inflamm Res

Publisher Dove Medical Press

Date 2025 Jan 13

PMID 39802506

Authors

Xiaoyu Huang

Gang Peng

Yaqing Kong

Xiaojing Cao

Xiang Zhou

Affiliations

Soon will be listed here.

Abstract

Purpose: This study aimed to evaluate the prognostic value of C-reactive protein to albumin (CRP/Alb) ratio in hepatocellular carcinoma (HCC) treated with transcatheter intra-arterial therapy combined with molecular targeted agents (MTAs) and programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors.

Methods: Medical records of 271 consecutive patients with HCC receiving this combination therapy in China between 2019 and 2023 were retrospectively analyzed. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were identified using univariate and multivariate Cox regression analyses. The discriminatory capability of inflammation-based prognostic scores-including the CRP/Alb ratio, C-reactive protein and alpha-fetoprotein in immunotherapy (CRAFITY) score, modified Glasgow prognostic score (mGPS), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII)-was assessed using the area under the curve (AUC).

Results: A total of 133 patients met the inclusion criteria. The optimal cutoff value for the binary classification of CRP/Alb ratio in predicting OS, as determined using X-tile software, was 0.02. Multivariate analysis identified the CRP/Alb ratio (hazard ratio [HR] = 2.61, < 0.001), tumor size (HR = 2.45, = 0.018), and extrahepatic metastases (HR = 1.93, = 0.015) as independent predictors of OS. For PFS, significant factors included Eastern Cooperative Oncology Group Performance Status (HR = 1.55, = 0.033) and macrovascular invasion (HR = 1.48, = 0.046). Patients with higher CRP/Alb ratios were more likely to experience fever and fatigue. The CRP/Alb ratio demonstrated significantly higher AUCs than PLR and SII at 24 months (all < 0.05) and showed comparable AUCs to CRAFITY score and mGPS at 12, 24, and 36 months.

Conclusion: The CRP/Alb ratio is a valuable prognostic marker for predicting OS and treatment-related adverse events in HCC patients receiving transcatheter intra-arterial therapy combined with MTAs and PD-1/PD-L1 inhibitors. This ratio can be used as a simple and reliable biomarker for assessing prognosis and guiding patient selection in clinical practice.

References

Casadei-Gardini A, Rimini M, Tada T, Suda G, Shimose S, Kudo M . Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population. Eur J Cancer. 2022; 180:9-20. DOI: 10.1016/j.ejca.2022.11.017. View

Zhu H, Li H, Huang M, Yang W, Yin G, Zhong B . Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001). Signal Transduct Target Ther. 2023; 8(1):58. PMC: 9905571. DOI: 10.1038/s41392-022-01235-0. View

Pang S, Zhou Z, Yu X, Wei S, Chen Q, Nie S . The predictive value of integrated inflammation scores in the survival of patients with resected hepatocellular carcinoma: A Retrospective Cohort Study. Int J Surg. 2017; 42:170-177. DOI: 10.1016/j.ijsu.2017.04.018. View

Zhang T, Geng Z, Zuo M, Li J, Huang J, Huang Z . Camrelizumab (a PD-1 inhibitor) plus apatinib (an VEGFR-2 inhibitor) and hepatic artery infusion chemotherapy for hepatocellular carcinoma in Barcelona Clinic Liver Cancer stage C (TRIPLET): a phase II study. Signal Transduct Target Ther. 2023; 8(1):413. PMC: 10603153. DOI: 10.1038/s41392-023-01663-6. View

Yoshida T, Ichikawa J, Giuroiu I, Laino A, Hao Y, Krogsgaard M . C reactive protein impairs adaptive immunity in immune cells of patients with melanoma. J Immunother Cancer. 2020; 8(1). PMC: 7204799. DOI: 10.1136/jitc-2019-000234. View

Kudo M . Immune Checkpoint Inhibitors plus Anti-VEGF/Tyrosine Kinase Inhibitors Combined with TACE (Triple Therapy) in Unresectable Hepatocellular Carcinoma. Liver Cancer. 2024; 13(3):227-234. PMC: 11185853. DOI: 10.1159/000538558. View

Liu J, Wang P, Shang L, Zhang Z, Tian Y, Chen X . TACE plus tyrosine kinase inhibitors and immune checkpoint inhibitors versus TACE plus tyrosine kinase inhibitors for the treatment of patients with hepatocellular carcinoma: a meta-analysis and trial sequential analysis. Hepatol Int. 2023; 18(2):595-609. DOI: 10.1007/s12072-023-10591-0. View

Lencioni R, Llovet J . Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010; 30(1):52-60. DOI: 10.1055/s-0030-1247132. View

Reig M, Forner A, Rimola J, Ferrer-Fabrega J, Burrel M, Garcia-Criado A . BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol. 2021; 76(3):681-693. PMC: 8866082. DOI: 10.1016/j.jhep.2021.11.018. View

10.

Kudo M, Kawamura Y, Hasegawa K, Tateishi R, Kariyama K, Shiina S . Management of Hepatocellular Carcinoma in Japan: JSH Consensus Statements and Recommendations 2021 Update. Liver Cancer. 2021; 10(3):181-223. PMC: 8237791. DOI: 10.1159/000514174. View

11.

Camp R, Dolled-Filhart M, Rimm D . X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res. 2004; 10(21):7252-9. DOI: 10.1158/1078-0432.CCR-04-0713. View

12.

Gordan J, Kennedy E, Abou-Alfa G, Beal E, Finn R, Gade T . Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update. J Clin Oncol. 2024; 42(15):1830-1850. DOI: 10.1200/JCO.23.02745. View

13.

Gupta D, Lis C . Pretreatment serum albumin as a predictor of cancer survival: a systematic review of the epidemiological literature. Nutr J. 2010; 9:69. PMC: 3019132. DOI: 10.1186/1475-2891-9-69. View

14.

Li Y, Guo J, Liu W, Pang H, Song Y, Wu S . Hepatic artery infusion chemotherapy combined with camrelizumab plus rivoceranib for hepatocellular carcinoma with portal vein tumor thrombosis: a multicenter propensity score-matching analysis. Hepatol Int. 2024; 18(4):1286-1298. PMC: 11297837. DOI: 10.1007/s12072-024-10672-8. View

15.

Lewandowski R, Geschwind J, Liapi E, Salem R . Transcatheter intraarterial therapies: rationale and overview. Radiology. 2011; 259(3):641-57. PMC: 3400295. DOI: 10.1148/radiol.11081489. View

16.

Zuo M, Zheng G, Cao Y, Lu H, Li D, An C . Hepatic arterial chemotherapy infusion combined with tyrosine kinase inhibitors and PD-1 inhibitors for advanced hepatocellular carcinoma with high risk: a propensity score matching study. Int J Surg. 2024; 111(1):104-112. PMC: 11745606. DOI: 10.1097/JS9.0000000000001940. View

17.

Fu Y, Peng W, Zhang W, Yang Z, Hu Z, Pang Y . Induction therapy with hepatic arterial infusion chemotherapy enhances the efficacy of lenvatinib and pd1 inhibitors in treating hepatocellular carcinoma patients with portal vein tumor thrombosis. J Gastroenterol. 2023; 58(4):413-424. DOI: 10.1007/s00535-023-01976-x. View

18.

Rimassa L, Finn R, Sangro B . Combination immunotherapy for hepatocellular carcinoma. J Hepatol. 2023; 79(2):506-515. DOI: 10.1016/j.jhep.2023.03.003. View

19.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

20.

de Castro T, Welland S, Jochheim L, Leyh C, Shmanko K, Finkelmeier F . Atezolizumab/bevacizumab and lenvatinib for hepatocellular carcinoma: A comparative analysis in a European real-world cohort. Hepatol Commun. 2024; 8(11). PMC: 11537570. DOI: 10.1097/HC9.0000000000000562. View