CONUT Score Predicts Early Morbidity After Liver Transplantation: A Collaborative Study

Gabriele Spoletini, Flaminia Ferri, Alberto Mauro, Gianluca Mennini, Giuseppe Bianco, Vincenzo Cardinale, Salvatore Agnes, Massimo Rossi, Alfonso Wolfango Avolio, Quirino Lai, Gabriele Spoletini, Flaminia Ferri, Alberto Mauro, Gianluca Mennini, Giuseppe Bianco, Vincenzo Cardinale, Salvatore Agnes, Massimo Rossi, Alfonso Wolfango Avolio, Quirino Lai

Abstract

Introduction: Liver transplantation (LT) is burdened by the risk of post-operative morbidity. Identifying patients at higher risk of developing complications can help allocate resources in the perioperative phase. Controlling Nutritional Status (CONUT) score, based on lymphocyte count, serum albumin, and cholesterol levels, has been applied to various surgical specialties, proving reliable in predicting complications and prognosis. Our study aims to investigate the role of the CONUT score in predicting the development of early complications (within 90 days) after LT. Methods: This is a retrospective analysis of 209 patients with a calculable CONUT score within 2 months before LT. The ability of the CONUT score to predict severe complications, defined as a Comprehensive Complication Index (CCI) ≥42.1, was examined. Inverse Probability Treatment Weighting was used to balance the study population against potential confounders. Results: Patients with a CCI ≥42.1 had higher CONUT score values (median: 7 vs. 5, P-value < 0.0001). The CONUT score showed a good diagnostic ability regarding post-LT morbidity, with an AUC = 0.72 (95.0%CI = 0.64-0.79; P-value < 0.0001). The CONUT score was the only independent risk factor identified for a complicated post-LT course, with an odds ratio = 1.39 (P-value < 0.0001). The 90-day survival rate was 98.8% and 87.5% for patients with a CONUT score <8 and ≥8, respectively. Conclusions: Pre-operative CONUT score is a helpful tool to identify patients at increased post-LT morbidity risk. Further refinements in the score composition, specific to the LT population, could be obtained with prospective studies.

Keywords: albumin; cholesterol; immunology; liver transplant complications; lymphocyte count; nutrition; post-operative morbidity.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Spoletini, Ferri, Mauro, Mennini, Bianco, Cardinale, Agnes, Rossi, Avolio and Lai.

Figures

Figure 1
Figure 1
Median and IQR values of CONUT in the low- and high-CCI groups.
Figure 2
Figure 2
Linear correlation between CONUT and CCI.
Figure 3
Figure 3
Harrel's c-statistics for the diagnosis of CCI ≥42.1.
Figure 4
Figure 4
Kaplan-Maier analysis for the 90-day patient survival rates in patient initially with CONUT 0–7 vs 8–12.

References

    1. Kardashian A, Ge J, McCulloch CE, Kappus MR, Dunn MA, Duarte-Rojo A, et al. . Identifying an optimal liver frailty index cutoff to predict waitlist mortality in liver transplant candidates. Hepatol Baltim Md. (2021) 73:1132–9. 10.1002/hep.31406
    1. Guijo-Rubio D, Briceño J, Gutiérrez PA, Ayllón MD, Ciria R, Hervás-Martínez C. Statistical methods versus machine learning techniques for donor-recipient matching in liver transplantation. PLoS ONE. (2021) 16:e0252068. 10.1371/journal.pone.0252068
    1. Skipworth JR, Spoletini G, Imber C. Surgical issues in retrieval and implantation. Br J Hosp Med Lond Engl. (2017) 78:266–72. 10.12968/hmed.2017.78.5.266
    1. Agopian VG, Harlander-Locke MP, Markovic D, Dumronggittigule W, Xia V, Kaldas FM, et al. . Evaluation of early allograft function using the liver graft assessment following transplantation risk score model. JAMA Surg. (2018) 153:436–44. 10.1001/jamasurg.2017.5040
    1. Avolio AW, Franco A, Schlegel A, Lai Q, Meli S, Burra P, et al. . Development and validation of a comprehensive model to estimate early allograft failure among patients requiring early liver retransplant. JAMA Surg. (2020) 155:e204095. 10.1001/jamasurg.2020.4095
    1. Pravisani R, Mocchegiani F, Isola M, Lorenzin D, Adani GL, Cherchi V, et al. . Controlling Nutritional Status score does not predict patients' overall survival or hepatocellular carcinoma recurrence after deceased donor liver transplantation. Clin Transplant. (2020) 34:e13786. 10.1111/ctr.13786
    1. Raveh Y, Livingstone J, Mahan J, Tekin A, Selvaggi G, Bowdon-Romero M, et al. . Comprehensive frailty severity index for end-stage liver disease predicts early outcomes after liver transplantation. JPEN J Parenter Enteral Nutr. (2020) 44:1079–88. 10.1002/jpen.1729
    1. Amygdalos I, Bednarsch J, Meister FA, Erren D, Mantas A, Strnad P, et al. . Clinical value and limitations of the pre-operative C-reactive-protein-to-albumin ratio in predicting postoperative morbidity and mortality after deceased-donor liver transplantation: a retrospective single-centre study. Transpl Int Off J Eur Soc Organ Transplant. (2021) 34:1468–80 10.1111/tri.13957
    1. Jin H, Zhu K, Wang W. The predictive values of pretreatment Controlling Nutritional Status (CONUT) score in estimating short- and long-term outcomes for patients with gastric cancer treated with neoadjuvant chemotherapy and curative gastrectomy. J Gastric Cancer. (2021) 21:155–68. 10.5230/jgc.2021.21.e14
    1. Wang A, He Z, Cong P, Qu Y, Hu T, Cai Y, et al. . Controlling Nutritional Status (CONUT) score as a new indicator of prognosis in patients with hilar cholangiocarcinoma is superior to NLR and PNI: a single-center retrospective study. Front Oncol. (2020) 10:593452. 10.3389/fonc.2020.593452
    1. Müller L, Hahn F, Mähringer-Kunz A, Stoehr F, Gairing SJ, Foerster F, et al. . Immunonutritive scoring in patients with hepatocellular carcinoma undergoing transarterial chemoembolization: prognostic nutritional index or controlling nutritional status score? Front Oncol. (2021) 11:696183. 10.3389/fonc.2021.696183
    1. Ignacio de. Ulíbarri J, González-Madroño A, de Villar NGP, González P, González B, Mancha A, et al. CONUT: a tool for controlling nutritional status First validation in a hospital population. Nutr Hosp. (2005) 20:38–45.
    1. Yagi T, Oshita Y, Okano I, Kuroda T, Ishikawa K, Nagai T, et al. . Controlling nutritional status score predicts postoperative complications after hip fracture surgery. BMC Geriatr. (2020) 20:243. 10.1186/s12877-020-01643-3
    1. Shiihara M, Higuchi R, Izumo W, Yazawa T, Uemura S, Furukawa T, et al. . Impact of the controlling nutritional status score on severe postoperative complications of pancreaticoduodenectomy for pancreatic cancer. Langenbecks Arch Surg. (2021) 406:1491–8. 10.1007/s00423-021-02151-7
    1. Dong X, Tang S, Liu W, Qi W, Ye L, Yang X, et al. . Prognostic significance of the Controlling Nutritional Status (CONUT) score in predicting postoperative complications in patients with Crohn's disease. Sci Rep. (2020) 10:19040. 10.1038/s41598-020-76115-0
    1. Yoshida N, Baba Y, Shigaki H, Harada K, Iwatsuki M, Kurashige J, et al. . Preoperative nutritional assessment by Controlling Nutritional Status (CONUT) is useful to estimate postoperative morbidity after esophagectomy for esophageal cancer. World J Surg. (2016) 40:1910–7. 10.1007/s00268-016-3549-3
    1. Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, et al. . The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. (2009) 250:187–96. 10.1097/SLA.0b013e3181b13ca2
    1. Slankamenac K, Graf R, Barkun J, Puhan MA, Clavien P-A. The comprehensive complication index: a novel continuous scale to measure surgical morbidity. Ann Surg. (2013) 258:1–7. 10.1097/SLA.0b013e318296c732
    1. Lai Q, Melandro F, Nowak G, Nicolini D, Iesari S, Fasolo E, et al. . The role of the comprehensive complication index for the prediction of survival after liver transplantation. Updat Surg. (2021) 73:209–21. 10.1007/s13304-020-00878-4
    1. Muller X, Marcon F, Sapisochin G, Marquez M, Dondero F, Rayar M, et al. . Defining benchmarks in liver transplantation: a multicenter outcome analysis determining best achievable results. Ann Surg. (2018) 267:419–25. 10.1097/SLA.0000000000002477
    1. Zhang Z. Missing data imputation: focusing on single imputation. Ann Transl Med. (2016) 4:9. 10.3978/j.issn.2305-5839.2015.12.38
    1. Burnand B, Kernan WN, Feinstein AR. Indexes and boundaries for quantitative significance in statistical decisions. J Clin Epidemiol. (1990) 43:1273–84. 10.1016/0895-4356(90)90093-5
    1. Fozouni L, Mohamad Y, Lebsack A, Freise C, Stock P, Lai JC. Frailty is associated with increased rates of acute cellular rejection within 3 months after liver transplantation. Liver Transplant Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc. (2020) 26:390–6. 10.1002/lt.25669
    1. Burra P, Samuel D, Sundaram V, Duvoux C, Petrowsky H, Terrault N, et al. . Limitations of current liver donor allocation systems and the impact of newer indications for liver transplantation. J Hepatol. (2021) 75 Suppl 1:S178–90. 10.1016/j.jhep.2021.01.007
    1. Li L, Liu C, Yang J, Wu H, Wen T, Wang W, et al. . Early postoperative controlling nutritional status (CONUT) score is associated with complication III-V after hepatectomy in hepatocellular carcinoma: a retrospective cohort study of 1,334 patients. Sci Rep. (2018) 8:13406. 10.1038/s41598-018-31714-w
    1. Miyata T, Yamashita Y-I, Higashi T, Taki K, Izumi D, Kosumi K, et al. . The prognostic impact of Controlling Nutritional Status (CONUT) in intrahepatic cholangiocarcinoma following curative hepatectomy: a retrospective single institution study. World J Surg. (2018) 42:1085–91. 10.1007/s00268-017-4214-1
    1. Harimoto N, Yoshizumi T, Inokuchi S, Itoh S, Adachi E, Ikeda Y, et al. . Prognostic significance of preoperative Controlling Nutritional Status (CONUT) score in patients undergoing hepatic resection for hepatocellular carcinoma: a multi-institutional study. Ann Surg Oncol. (2018) 25:3316–23. 10.1245/s10434-018-6672-6
    1. Iseki Y, Shibutani M, Maeda K, Nagahara H, Ohtani H, Sugano K, et al. . Impact of the preoperative Controlling Nutritional Status (CONUT) score on the survival after curative surgery for colorectal cancer. PLoS ONE. (2015) 10:e0132488. 10.1371/journal.pone.0132488
    1. Toyokawa T, Kubo N, Tamura T, Sakurai K, Amano R, Tanaka H, et al. . The pretreatment Controlling Nutritional Status (CONUT) score is an independent prognostic factor in patients with resectable thoracic esophageal squamous cell carcinoma: results from a retrospective study. BMC Cancer. (2016) 16:722. 10.1186/s12885-016-2696-0
    1. Toyokawa G, Kozuma Y, Matsubara T, Haratake N, Takamori S, Akamine T, et al. . Prognostic impact of controlling nutritional status score in resected lung squamous cell carcinoma. J Thorac Dis. (2017) 9:2942–51. 10.21037/jtd.2017.07.108
    1. Kuroda D, Sawayama H, Kurashige J, Iwatsuki M, Eto T, Tokunaga R, et al. . Controlling Nutritional Status (CONUT) score is a prognostic marker for gastric cancer patients after curative resection. Gastric Cancer Off J Int Gastric Cancer Assoc Jpn Gastric Cancer Assoc. (2018) 21:204–12. 10.1007/s10120-017-0744-3
    1. Ishihara H, Kondo T, Yoshida K, Omae K, Takagi T, Iizuka J, et al. . Pre-operative controlling nutritional status (CONUT) score as a novel predictive biomarker of survival in patients with localized urothelial carcinoma of the upper urinary tract treated with radical nephroureterectomy. Urol Oncol. (2017) 35:539.e9–16. 10.1016/j.urolonc.2017.04.012
    1. Pravisani R, Mocchegiani F, Isola M, Lorenzin D, Adani GL, Cherchi V, et al. . Postoperative trends and prognostic values of inflammatory and nutritional biomarkers after liver transplantation for hepatocellular carcinoma. Cancers. (2021) 13:513. 10.3390/cancers13030513
    1. Nishikawa H, Yoh K, Enomoto H, Ishii N, Iwata Y, Takata R, et al. . The Relationship between Controlling Nutritional (CONUT) score and clinical markers among adults with hepatitis C virus related liver cirrhosis. Nutrients. (2018) 10:1185. 10.3390/nu10091185
    1. Takamori S, Toyokawa G, Taguchi K, Edagawa M, Shimamatsu S, Toyozawa R, et al. . The controlling nutritional status score is a significant independent predictor of poor prognosis in patients with malignant pleural mesothelioma. Clin Lung Cancer. (2017) 18:e303–13. 10.1016/j.cllc.2017.01.008
    1. Lai JC, Covinsky KE, Dodge JL, Boscardin WJ, Segev DL, Roberts JP, et al. . Development of a novel frailty index to predict mortality in patients with end-stage liver disease. Hepatol Baltim Md. (2017) 66:564–74. 10.1002/hep.29219
    1. Duarte-Rojo A, Ruiz-Margáin A, Montaño-Loza AJ, Macías-Rodríguez RU, Ferrando A, Kim WR. Exercise and physical activity for patients with end-stage liver disease: Improving functional status and sarcopenia while on the transplant waiting list. Liver Transplant. (2018) 24:122–39. 10.1002/lt.24958
    1. Lai Q, Magistri P, Lionetti R, Avolio AW, Lenci I, Giannelli V, et al. . Sarco-model: a score to predict the dropout risk in the perspective of organ allocation in patients awaiting liver transplantation. Liver Int. (2021) 41:1629–40. 10.1111/liv.14889
    1. Lin F-P, Visina JM, Bloomer PM, Dunn MA, Josbeno DA, Zhang X, et al. . Prehabilitation-driven changes in frailty metrics predict mortality in patients with advanced liver disease. Am J Gastroenterol. (2021) 116:2105–17 10.14309/ajg.0000000000001376
    1. Xu CQ, Mohamad Y, Kappus MR, Boyarsky B, Ganger DR, Volk ML, et al. . The relationship between frailty and cirrhosis etiology: from the Functional Assessment in Liver Transplantation (FrAILT) Study. Liver Int Off J Int Assoc Study Liver. (2021) 41:2467–73 10.1111/liv.15006
    1. O'Brien AJ, Fullerton JN, Massey KA, Auld G, Sewell G, James S, et al. . Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin E2. Nat Med. (2014) 20:518–23. 10.1038/nm.3516
    1. Katsiki N, Mikhailidis DP, Mantzoros CS. Non-alcoholic fatty liver disease and dyslipidemia: an update. Metabolism. (2016) 65:1109–23. 10.1016/j.metabol.2016.05.003

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe