Carr B.I.a· Guerra V.b

Author affiliations

aLiver Transplant Institute, Inonu University Faculty of Medicine, Malatya, Turkey
bNational Institute of Gastroenterology, S. de Bellis Research Hospital, Bari, Italy

Log in to MyKarger to check if you already have access to this content.

Buy FullText & PDF Unlimited re-access via MyKarger Unrestricted printing, no saving restrictions for personal use read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!

If you would like to redeem your KAB credit, please log in.

Save over 20% compared to the individual article price.

Learn more

Rent via DeepDyve Unlimited fulltext viewing of this article Organize, annotate and mark up articles Printing and downloading restrictions apply

Start free trial

Subscribe Access to all articles of the subscribed year(s) guaranteed for 5 years Unlimited re-access via Subscriber Login or MyKarger Unrestricted printing, no saving restrictions for personal use read more

Subcription rates

Select

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview

Received: August 22, 2022
Accepted: October 10, 2022
Published online: March 06, 2023

Number of Print Pages: 8
Number of Figures: 1
Number of Tables: 6

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: https://www.karger.com/OCL

Abstract

Introduction: Many single and combination blood tests that reflect local or systemic inflammation have been shown to be useful prognosticators in patients with a variety of tumor types. To try to clarify, this issue in patients with nonsurgically treatable hepatocellular carcinoma, multiple serum parameters were evaluated for their relationship to survival. Methods: A prospectively collected database was interrogated of 487 patients with known hepatocellular carcinoma and documented survival and having all the inflammation parameters of interest in this study, together with baseline tumor characteristics from CT scans. Serum parameters included NLR, PLR, CRP, ESR, albumin, and GGT. Results: All the parameters had significant hazard ratios on Cox regression model. Combination double parameters with hazard ratios >2.0 were: ESR plus GGT, albumin plus GGT, albumin plus ESR. The triplet combination of albumin plus GGT plus ESR had a hazard ratio of 6.33. Using Harrell’s concordance index (C-index), the highest inflammation-based 2-parameter prognostic score was for albumin plus GGT. When clinical characteristics of patients with high values for albumin plus low values for GGT were compared to low values for albumin plus high values for GGT (worse prognosis), statistically significant differences were found for tumor size, tumor focality, macroscopic portal vein invasion, and serum alpha-fetoprotein levels. Addition of ESR did not provide additional tumor information. Conclusion: The combination of serum albumin plus GGT levels was the most prognostically useful among the inflammation parameters that were tested, and reflected significant differences in tumor aggressiveness characteristics.

© 2023 S. Karger AG, Basel

References Virchow RLK. Die krankhaften Geschwülste. Berlin: August Hirschwald; 1863. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74. Refolo MG, Messa C, Guerra V, Carr BI, D’Alessandro R. Inflammatory mechanisms of HCC development. Cancers. 2020;12(3):641. Sengez B, Carr BI, Alotaibi H. EMT and inflammation: crossroads in HCC. J Gastrointest Cancer. 2022 Jan 12. DOI: 10.1007/s12029-021-00801-z. Suner A, Carr BI, Akkiz H, Uskudar O, Kuran S, Tokat Y, et al. Inflammatory markers C-reactive protein and PLR in relation to HCC characteristics. J Transl Sci. 2019;5(3). Fabris C, Pirisi M, Soardo G, Toniutto P, Falleti E, Vitulli D, et al. Diagnostic usefulness of acute-phase protein measurement in hepatocellular carcinoma. Cancer Invest. 1996;14(2):103–8. Carr BI, Akkiz H, Guerra V, Üsküdar O, Kuran S, Karaoğullarından U, et al. C-reactive protein and hepatocellular carcinoma: analysis of its relationships to tumor factors. Clin Pract. 2018;15(Spec Issue):625–34. Shiba H, Horiuchi T, Sakamoto T, Furukawa K, Shirai Y, Iida T, et al. Glasgow prognostic score predicts therapeutic outcome after hepatic resection for hepatocellular carcinoma. Oncol Lett. 2017;14(1):293–8. Carr BI, Akkiz H, Bag HG, Guerra V, Donghia R, Yalcin K, et al. Erythrocyte sedimentation rate and gamma-glutamyl transpeptidase combined are potent predictors of survival and tumor characteristics in hepatocellular carcinoma patients. J Clin Trials. 2020;10:425–32. Yamamoto M, Kobayashi T, Kuroda S, Hamaoka M, Okimoto S, Honmyo N, et al. Verification of inflammation-based prognostic marker as a prognostic indicator in hepatocellular carcinoma. Ann Gastroenterol Surg. 2019;3(6):667–75. Xu L, Yu S, Zhuang L, Wang P, Shen Y, Lin J, et al. Systemic inflammation response index (SIRI) predicts prognosis in hepatocellular carcinoma patients. Oncotarget. 2017;8(21):34954–60. Carr BI, Guerra V. Serum albumin levels in relation to tumor parameters in hepatocellular carcinoma patients. Int J Biol Markers. 2017 Oct 31;32(4):e391–6. Akkiz H, Carr BI, Bag HG, Karaoğullarından Ü, Yalçın K, Ekin N, et al. Serum levels of inflammatory markers CRP, ESR and albumin in relation to survival for patients with hepatocellular carcinoma. Int J Clin Pract. 2021 Feb;75(2):e13593. Ke Q, Xiang F, Xiao C, Huang Q, Liu X, Zeng Y, et al. Exploring the clinical value of preoperative serum gamma-glutamyl transferase levels in the management of patients with hepatocellular carcinoma receiving postoperative adjuvant transarterial chemoembolization. BMC Cancer. 2021 Oct 18;21(1):1117. Newson R. Efficient calculation of jackknife confidence intervals for rank statistics. J Stat Softw. 2006;15:1–10. Hernandez-Gea V, Toffanin S, Friedman SL, Llovet JM. Role of the microenvironment in the pathogenesis and treatment of hepatocellular carcinoma. Gastroenterology. 2013;144(3):512–27. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357(9255):539–45. Utsumi M, Kitada K, Tokunaga N, Narusaka T, Hamano R, Miyasou H, et al. Preoperative albumin-to-globulin ratio predicts prognosis in hepatocellular carcinoma: a cohort study including non-hepatitis virus-infected patients. Dig Surg. 2021;38(4):307–15. Shen X, Wang W, Niu X. Neutrophil lymphocyte ratio to albumin ratio and white blood cell to hemoglobin ratio as prognostic markers for hepatocellular carcinoma patients who underwent curative hepatectomy. Int J Gen Med. 2021 Aug 29;14:5029–38. Chen S, Ma W, Cao F, Shen L, Qi H, Xie L, et al. Hepatocellular carcinoma within the milan criteria: a novel inflammation-based nomogram system to assess the outcomes of ablation. Front Oncol. 2020 Sep 14;10:1764. Shen J, Tang L, Zhang X, Peng W, Wen T, Li C, et al. A novel index in hepatocellular carcinoma patients after curative hepatectomy: albumin to gamma- glutamyltransferase ratio (AGR). Front Oncol. 2019 Sep 4;9:817. Shen Y, Wang H, Li W, Chen J. Prognostic significance of the CRP/Alb and neutrophil to lymphocyte ratios in hepatocellular carcinoma patients undergoing TACE and RFA. J Clin Lab Anal. 2019 Nov;33(9):e22999. Ren Y, Fan X, Chen G, Zhou D, Lin H, Cai X. Preoperative C-reactive protein/albumin ratio to predict mortality and recurrence of patients with hepatocellular carcinoma after curative resection. Med Clin. 2019 Sep 13;153(5):183–90. Suner A, Carr BI, Akkiz H, Karakülah G, Üsküdar O, Yalçın K, et al. C-reactive protein and platelet-lymphocyte ratio as potential tumor markers in low-alpha- fetoprotein hepatocellular carcinoma. Oncology. 2019;96(1):25–32. Casadei Gardini A, Foschi FG, Conti F, Petracci E, Vukotic R, Marisi G, et al. Immune inflammation indicators and ALBI score to predict liver cancer in HCV-patients treated with direct-acting antivirals. Dig Liver Dis. 2019 May;51(5):681–8. Gkika E, Bettinger D, Krafft L, Schultheiss M, Neeff HP, Maruschke L, et al. The role of albumin-bilirubin grade and inflammation-based index in patients with hepatocellular carcinoma treated with stereotactic body radiotherapy. Strahlenther Onkol. 2018 May;194(5):403–13. Shimizu T, Ishizuka M, Suzuki T, Tanaka G, Park KH, Matsumoto T, et al. The preoperative globulin-to-albumin ratio, a novel inflammation-based prognostic system, predicts survival after potentially curative liver resection for patients with hepatocellular carcinoma. J Surg Oncol. 2017 Dec;116(8):1166–75. Bağırsakçı E, Şahin E, Atabey N, Erdal E, Guerra V, Carr BI. Role of albumin in growth inhibition in hepatocellular carcinoma. Oncology. 2017;93(2):136–42. Kinoshita A, Onoda H, Imai N, Iwaku A, Oishi M, Tanaka K, et al. The C-reactive protein/albumin ratio, a novel inflammation-based prognostic score, predicts outcomes in patients with hepatocellular carcinoma. Ann Surg Oncol. 2015 Mar;22(3):803–10. Pinato DJ, North BV, Sharma R. A novel, externally validated inflammation- based prognostic algorithm in hepatocellular carcinoma: the prognostic nutritional index (PNI). Br J Cancer. 2012 Apr 10;106(8):1439–45. Kinoshita A, Onoda H, Imai N, Iwaku A, Oishi M, Tanaka K, et al. The Glasgow Prognostic Score, an inflammation based prognostic score, predicts survival in patients with hepatocellular carcinoma. BMC Cancer. 2013 Feb 2;13:52. NojiriJoh ST. Albumin suppresses human hepatocellular carcinoma proliferation and the cell cycle. Int J Mol Sci. 2014;15(3):5163–74. Arroyo V, García-Martinez R, Salvatella X. Human serum albumin, systemic inflammation, and cirrhosis. J Hepatol. 2014;61(2):396–407. Smith C, Halliwell B, Aruoma OI. Protection by albumin against the pro-oxidant actions of phenolic dietary components. Food Chem Toxicol. 1992;30(6):483–9. Liu W, Zhang F, Quan B, Li M, Lu S, Li J, et al. The prognostic value of the albumin to gamma-glutamyltransferase ratio in patients with hepatocellular carcinoma undergoing radiofrequency ablation. Dis Markers. 2021;2021:3514827. Bi C, Akkiz H, Hg B, Karaoğullarından U, Yalçın K, Ekin N, et al. Serum levels of gamma-glutamyl transpeptidase in relation to HCC human biology and prognosis. J Transl Sci. 2021 Jun;7(3). Orzechowska D, Klimowicz K, Stępień A, Mikuła T, Sapuła M, Wiercińska-Drapało . Change in γ-glutamyl transpeptidase activity as a useful tool in identifying a group of patients with elevated risk of hepatocellular carcinoma development after DAA treatment of chronic hepatitis C. Clin Exp Hepatol. 2021 Mar;7(1):93–100. Yang D, Wu H, Nong W, Zheng M, Li A, Wang Y, et al. A new model based on gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts prognostic outcome after curative resection of solitary hepatocellular carcinoma. Clin Res Hepatol Gastroenterol. 2021 Sep;45(5):101509. Ince V, Carr BI, Bag HG, Ersan V, Usta S, Koc C, et al. Liver transplant for large hepatocellular carcinoma in Malatya: the role of gamma glutamyl transferase and alpha-fetoprotein, a retrospective cohort study. World J Gastrointest Surg. 2020 Dec 27;12(12):520–533. Carr BI, Ince V, Bag HG, Ersan V, Usta S, Yilmaz S. Microscopic vascular invasion by hepatocellular carcinoma in liver transplant patients. Clin Pract. 2020;17(3):1497–505. Guo J, Liu S, Gao S, Kou F, Zhang X, Liu P, et al. γ-Glutamyltranspeptidase as a prognostic biomarker in advanced hepatocellular carcinoma treated with transarterial chemoembolization. J Vasc Interv Radiol. 2021 Mar;32(3):419–28.e2. Ma H, Zhang L, Tang B, Wang Y, Chen R, Zhang B, et al. γ-Glutamyltranspeptidase is a prognostic marker of survival and recurrence in radiofrequency-ablation treatment of hepatocellular carcinoma. Ann Surg Oncol. 2014 Sep;21(9):3084–9. Wang Y, Sun K, Shen J, Li B, Kuang M, Cao Q, et al. Novel prognostic nomograms based on inflammation-related markers for patients with hepatocellular carcinoma underwent hepatectomy. Cancer Res Treat. 2019 Oct;51(4):1464–78. Shi S, Chen Q, Ye L, Yin D, Li X, Dai Z, et al. Prognostic value of systemic inflammation score in patients with hepatocellular carcinoma after hepatectomy. Oncotarget. 2017 May 24;8(45):79366–75. Carr BI, Guerra V, Giannini EG, Farinati F, Ciccarese F, Rapaccini GL, et al. Low alpha-fetoprotein HCC and the role of GGTP. Int J Biol Markers. 2014;29(4):e395–402. Hanigan MH. Gamma-glutamyl transpeptidase: redox regulation and drug resistance. Adv Cancer Res. 2014;122:103–41. Hanigan MH. Expression of gamma-glutamyl transpeptidase provides tumor cells with a selective growth advantage at physiologic concentrations of cyst(e)ine. Carcinogenesis. 1995;16(2):181–5. Vanderlaan M, Phares W. gamma-Glutamyltranspeptidase: a tumour cell marker with a pharmacological function. Histochem J. 1981;13(5):865–77. Article / Publication Details

First-Page Preview

Received: August 22, 2022
Accepted: October 10, 2022
Published online: March 06, 2023

Number of Print Pages: 8
Number of Figures: 1
Number of Tables: 6

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: https://www.karger.com/OCL

Copyright / Drug Dosage / Disclaimer Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.