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Fujiwara N, Trépo E, Raman I, et al. Plasma-Signature-Model for End-Stage Liver Disease Score to Predict Survival in Severe Alcoholic Hepatitis. Clin Gastroenterol Hepatol. 2021;doi: 10.1016/j.cgh.2021.02.041.
Fujiwara, N., Trépo, E., Raman, I., Li, Q. Z., Degré, D., Gustot, T., Moreno, C., & Hoshida, Y. (2021). Plasma-Signature-Model for End-Stage Liver Disease Score to Predict Survival in Severe Alcoholic Hepatitis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, . https://doi.org/10.1016/j.cgh.2021.02.041
Fujiwara, Naoto, et al. "Plasma-Signature-Model for End-Stage Liver Disease Score to Predict Survival in Severe Alcoholic Hepatitis." Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association vol. (2021). doi: https://doi.org/10.1016/j.cgh.2021.02.041
Fujiwara N, Trépo E, Raman I, Li QZ, Degré D, Gustot T, Moreno C, Hoshida Y. Plasma-Signature-Model for End-Stage Liver Disease Score to Predict Survival in Severe Alcoholic Hepatitis. Clin Gastroenterol Hepatol. 2021 Mar 02; doi: 10.1016/j.cgh.2021.02.041. Epub 2021 Mar 02. PMID: 33667676; PMCID: PMC8410886.
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Clin Gastroenterol Hepatol. 2021 Mar 02; doi: 10.1016/j.cgh.2021.02.041. Epub 2021 Mar 02.

Plasma-Signature-Model for End-Stage Liver Disease Score to Predict Survival in Severe Alcoholic Hepatitis.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

Naoto Fujiwara, Eric Trépo, Indu Raman, Quan-Zhen Li, Delphine Degré, Thierry Gustot, Christophe Moreno, Yujin Hoshida

Affiliations

  1. Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, Dallas, Texas; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  2. Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, Cliniques universitaires de Bruxelles Hôpital Erasme, Brussels, Belgium; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium.
  3. Microarray Core Facility, Department of Immunology, BioCenter, University of Texas Southwestern Medical Center, Dallas, Texas.
  4. Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, Dallas, Texas. Electronic address: [email protected].

PMID: 33667676 PMCID: PMC8410886 DOI: 10.1016/j.cgh.2021.02.041

Abstract

BACKGROUND & AIMS: Severe alcoholic hepatitis (AH) is a highly lethal condition and it is still a challenge to predict the outcome. We previously identified and validated a composite score of hepatic 123-gene prognostic signature and the model for end-stage liver disease (MELD) score: gene signature-MELD. However, the need for liver biopsy limits its clinical application. Therefore, we aimed to identify a plasma protein-based surrogate of the gene signature and independently validate its prognostic capability.

METHODS: All patients were diagnosed with severe AH at Cliniques universitaires de Bruxelles Hôpital Erasme (Brussels, Belgium), and the plasma samples were collected at admission before any treatment. The primary outcome was death or liver transplantation within 90 days. Using our computational pipeline, named translation of tissue expression to secretome (TexSEC), a hepatic-transcriptome-based prognostic signature was converted to a plasma-based secretome signature, which was optimized in 50 patients by comparing their hepatic molecular dysregulation status and combining it with the MELD score. The composite score was validated independently in 57 patients.

RESULTS: The TexSEC and optimization process identified a 6-plasma-protein panel as a surrogate for the 123-gene signature. A composite score with the MELD score, the plasma-signature (ps)-MELD score, was created by using the coefficients of the gene signature-MELD equation. In the validation cohort, the high-risk ps-MELD (n = 23; 40%) was associated significantly with death or liver transplantation within 90 days (adjusted hazard ratio, 4.57; 95% CI, 2.15-9.30; P < .001). The ps-MELD score showed a stable, high prognostic association (time-dependent area under receiver operating characteristics curve, >0.80) and was well calibrated over time; it consistently outperformed existing clinical scores as indicated by various model performance indices.

CONCLUSIONS: The high-risk ps-MELD score was associated with short-term survival in patients with severe AH.

Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.

Keywords: Biomarker; Death; Liver Transplantation; Severe Alcoholic Hepatitis

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