Development and Internal Validation of a Novel Pre-Transplant Biomarker Panel to Predict Post-Liver Transplant Mortality-Reference-Cited by-同舟云学术

Development and Internal Validation of a Novel Pre-Transplant Biomarker Panel to Predict Post-Liver Transplant Mortality

Published:2023-10-12 Issue: Volume: Page:
ISSN:
Container-title:
language:
Short-container-title:

Author:

Panayotova Guergana G.¹,Simonishvili Sopio¹,Nguyen Duc T.²,Graviss Edward A.²,Aware Nikita³,Manner Carl J.³,Minze Laurie J.³,Ayorinde Tumininu¹,Qin Yong¹,Jin Lianhua¹,Lemenze Alexander⁴,Mysore Krupa R.⁵,Moore Linda³,Paterno Flavio¹,Saharia Ashish³,Mobley Constance M.³,Amin Arpit¹,Hobeika Mark J.³,Pyrsopoulos Nikolaos⁶,Li Xian C.³,Guarrera James V.¹,Ghobrial R. Mark³,Lunsford Keri E.⁷

Affiliation:

1. Division of Liver Transplant and HPB Surgery, Department of Surgery, Rutgers New Jersey Medical School, Newark, NJ

2. Department of Pathology and Genomic Medicine, Houston Methodist Hospital and Research Institute, Houston, TX

3. Sherrie and Alan Conover Center for Liver Disease and Transplantation, J.C. Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX

4. Center for Immunity and Inflammation, Institute for Infectious and Inflammatory Diseases, Rutgers Biomedical and Health Sciences, Newark, NJ

5. Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX.

6. Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ

7. Division of Liver Transplant and HPB Surgery, Department of Surgery, Rutgers New Jersey Medical School, Newark, NJ and Center for Immunity and Inflammation, Institute for Infectious and Inflammatory Diseases, Rutgers Biomedical and Health Sciences, Newark, NJ

Abstract

Abstract Current scoring systems accurately predict risk of pre-liver transplant (LT) mortality but fall short in estimation of post-LT survival. This study seeks to identify biomarkers of pre-LT immune dysfunction that predict mortality following LT. From 10/1/13-3/23/21, 279 cirrhotic patients underwent assessment of plasma biomarker (Luminex) and clinical variables immediately prior to LT (T0). Cox-proportional hazards modeling identified HCV IgG, Fractalkine, and MMP3 as multivariate predictors of 1-year mortality, with covariate selection by clinical importance and LASSO methodology. These were utilized to comprise the novel Liver Immune Frailty Index (LIFI), which stratifies recipients into -low, -moderate, and –high risk tertiles. One-year mortality was 1.4%, 12.7%, and 58.3% for LIFI-low, -moderate, and -high, respectively. Internal validation through bootstrap resampling with 2000 replicates demonstrates LIFI predicts early post-LT mortality with C-statistic=0.84 and Brier score of 0.04. LIFI may identify patients at risk for persistent severe immune dysfunction and early mortality following LT.

Funder

National Institute of Diabetes and Digestive and Kidney Diseases

New Jersey Health Foundation

American Society of Transplant Surgeons

Publisher

Research Square Platform LLC

Reference95 articles.

1. Mortality due to cirrhosis and liver cancer in the United States, 1999–2016: observational study;Tapper EB;BMJ,2018

2. Wilde, B. & Katsounas, A. Immune Dysfunction and Albumin-Related Immunity in Liver Cirrhosis. Mediators Inflamm 2019, 7537649 (2019).

3. Kwong, A., et al. OPTN/SRTR 2018 Annual Data Report: Liver. Am J Transplant 20 Suppl s1, 193–299 (2020).

4. Code of Federal Regulation (CFR) annual edition. in Title 42: Public Health, Vol. Part 121 - Organ Procurement and Transplantationation Network (ed. Services, D.o.H.a.H.).

5. Model for end-stage liver disease (MELD) and allocation of donor livers;Wiesner R;Gastroenterology,2003