Inflammatory Markers Showed Significant Incremental Value for Predicting Post-Hepatectomy Liver Failure in Hepatocellular Carcinoma Patients

Overview

Journal Life (Basel)

Specialty Biology

Date 2023 Oct 28

PMID 37895372

Authors

Xiao Wang

Wenjun Wang

Xixiang Lin

Xu Chen

Mingxiang Zhu

Hongli Xu

Kunlun He

Affiliations

Soon will be listed here.

Abstract

Background: Post-hepatectomy liver failure (PHLF) remains a complication with the potential risk of mortality for hepatocellular carcinoma (HCC) patients. The systemic inflammatory response (SIR) has been demonstrated to be associated with a bad prognosis of liver cirrhosis and tumors. This study aims to evaluate the incremental prognostic value of inflammatory markers in predicting PHLF in patients with HCC.

Methods: Clinical characteristics and variables were retrospectively collected in 2824 patients diagnosed with HCC who underwent radical hepatectomy from the First Medical Center of the General Hospital of the People's Liberation Army. A recently published prognostic model for PHLF was used as the reference model. The increase in AUC (ΔAUC), integrated discrimination improvement (IDI), and the continuous version of the net reclassification improvement (NRI) were applied for quantifying the incremental value of adding the inflammatory markers to the reference model. A value < 0.05 was considered statistically significant.

Results: The reference PHLF model showed acceptable prediction performance in the current cohort, with an AUC of 0.7492 (95%CI, 0.7191-0.7794). The calculated ΔAUC associated with procalcitonin (PCT) was the only one that was statistically significant ( < 0.05), with a value of 0.0044, and demonstrated the largest magnitude of the increase in AUC. The continuous NRI value associated with the systemic immune-inflammation index (SII) was 35.79%, second only to GPS (46.07%). However, the inflammatory markers of the new models with statistically significant IDI only included WBC count, lymphocyte count, and SII. IDI associated with SII, meanwhile, was the maximum (0.0076), which was consistent with the performance of using the ΔAUC (0.0044) to assess the incremental value of each inflammatory variable.

Conclusions: Among a wide range of inflammatory markers, only PCT and SII have potential incremental prognostic value for predicting PHLF in patients with radical resectable HCC.

Citing Articles

Association between neutrophil percentage to albumin ratio and short term prognosis of acute on chronic liver failure treated with artificial liver support system.

Ma Y, Du L, Bai L, Tang H Sci Rep. 2025; 15(1):5042.

PMID: 39934390 PMC: 11814120. DOI: 10.1038/s41598-025-89832-1.

Are Ki-67 and Procalcitonin Expression Levels Useful in Predicting the Biological Behavior of Hepatocellular Carcinoma After Liver Transplantation?.

Karabulut E, Akbulut S, Samdanci E, Akatli A, Elsarawy A, Kucukakcali Z J Clin Med. 2025; 14(1.

PMID: 39797227 PMC: 11720816. DOI: 10.3390/jcm14010144.

Association between systemic immune inflammation index and short term prognosis of acute on chronic liver failure.

Ma Y, Xu Y, Du L, Bai L, Tang H Sci Rep. 2024; 14(1):21535.

PMID: 39278977 PMC: 11402960. DOI: 10.1038/s41598-024-72447-3.

References

Templeton A, McNamara M, Seruga B, Vera-Badillo F, Aneja P, Ocana A . Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014; 106(6):dju124. DOI: 10.1093/jnci/dju124. View

Fang L, Yan F, Liu C, Chen J, Wang D, Zhang C . Systemic Inflammatory Biomarkers, Especially Fibrinogen to Albumin Ratio, Predict Prognosis in Patients with Pancreatic Cancer. Cancer Res Treat. 2020; 53(1):131-139. PMC: 7811998. DOI: 10.4143/crt.2020.330. View

Pencina M, DAgostino Sr R, DAgostino Jr R, Vasan R . Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2007; 27(2):157-72. DOI: 10.1002/sim.2929. View

Wang C, He W, Yuan Y, Zhang Y, Li K, Zou R . Comparison of the prognostic value of inflammation-based scores in early recurrent hepatocellular carcinoma after hepatectomy. Liver Int. 2019; 40(1):229-239. DOI: 10.1111/liv.14281. View

Cannon N, Meyer J, Iyengar P, Ahn C, Westover K, Choy H . Neutrophil-lymphocyte and platelet-lymphocyte ratios as prognostic factors after stereotactic radiation therapy for early-stage non-small-cell lung cancer. J Thorac Oncol. 2014; 10(2):280-5. DOI: 10.1097/JTO.0000000000000399. View

Hsu C, Huang Y, Hsia C, Su C, Lin H, Loong C . A new prognostic model for hepatocellular carcinoma based on total tumor volume: the Taipei Integrated Scoring System. J Hepatol. 2010; 53(1):108-17. DOI: 10.1016/j.jhep.2010.01.038. View

Pepe M, Janes H, Longton G, Leisenring W, Newcomb P . Limitations of the odds ratio in gauging the performance of a diagnostic, prognostic, or screening marker. Am J Epidemiol. 2004; 159(9):882-90. DOI: 10.1093/aje/kwh101. View

Liu P, Hsu C, Hsia C, Lee Y, Su C, Huang Y . Prognosis of hepatocellular carcinoma: Assessment of eleven staging systems. J Hepatol. 2015; 64(3):601-8. DOI: 10.1016/j.jhep.2015.10.029. View

Kasymjanova G, Macdonald N, Agulnik J, Cohen V, Pepe C, Kreisman H . The predictive value of pre-treatment inflammatory markers in advanced non-small-cell lung cancer. Curr Oncol. 2010; 17(4):52-8. PMC: 2913830. DOI: 10.3747/co.v17i4.567. View

10.

Peng W, Zhang X, Li C, Wen T, Yan L, Yang J . Spleen stiffness and volume help to predict posthepatectomy liver failure in patients with hepatocellular carcinoma. Medicine (Baltimore). 2019; 98(18):e15458. PMC: 6504243. DOI: 10.1097/MD.0000000000015458. View

11.

Leening M, Vedder M, Witteman J, Pencina M, Steyerberg E . Net reclassification improvement: computation, interpretation, and controversies: a literature review and clinician's guide. Ann Intern Med. 2014; 160(2):122-31. DOI: 10.7326/M13-1522. View

12.

Njei B, Rotman Y, Ditah I, Lim J . Emerging trends in hepatocellular carcinoma incidence and mortality. Hepatology. 2014; 61(1):191-9. PMC: 4823645. DOI: 10.1002/hep.27388. View

13.

Kerr K, McClelland R, Brown E, Lumley T . Evaluating the incremental value of new biomarkers with integrated discrimination improvement. Am J Epidemiol. 2011; 174(3):364-74. PMC: 3202159. DOI: 10.1093/aje/kwr086. View

14.

Lau W, Lau S . The current role of radiofrequency ablation in the treatment of hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 2017; 16(2):122-126. DOI: 10.1016/s1499-3872(16)60182-0. View

15.

Bray F, Ferlay J, Soerjomataram I, Siegel R, Torre L, Jemal A . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6):394-424. DOI: 10.3322/caac.21492. View

16.

Mir Z, Golding H, McKeown S, Nanji S, Flemming J, Groome P . Appraisal of multivariable prognostic models for post-operative liver decompensation following partial hepatectomy: a systematic review. HPB (Oxford). 2021; 23(12):1773-1788. DOI: 10.1016/j.hpb.2021.06.430. View

17.

Meisner M . Pathobiochemistry and clinical use of procalcitonin. Clin Chim Acta. 2002; 323(1-2):17-29. DOI: 10.1016/s0009-8981(02)00101-8. View

18.

Xu M, Xu B, Zhou C, Xue Z, Chen Z, Xu W . An mALBI-Child-Pugh-based nomogram for predicting post-hepatectomy liver failure grade B-C in patients with huge hepatocellular carcinoma: a multi-institutional study. World J Surg Oncol. 2022; 20(1):206. PMC: 9202189. DOI: 10.1186/s12957-022-02672-5. View

19.

Pencina M, DAgostino Sr R, Demler O . Novel metrics for evaluating improvement in discrimination: net reclassification and integrated discrimination improvement for normal variables and nested models. Stat Med. 2011; 31(2):101-13. PMC: 3341978. DOI: 10.1002/sim.4348. View

20.

Abdel-Khalek E, El-Fakhry A, Helaly M, Hamed M, Elbaz O . Systemic inflammatory response syndrome in patients with liver cirrhosis. Arab J Gastroenterol. 2012; 12(4):173-7. DOI: 10.1016/j.ajg.2011.11.006. View