Combination of Gene Expression Signature and Model for End-Stage Liver Disease Score Predicts Survival of Patients With Severe Alcoholic Hepatitis

Eric Trépo, Nicolas Goossens, Naoto Fujiwara, Won Min Song, Antonio Colaprico, Astrid Marot, Laurent Spahr, Pieter Demetter, Christine Sempoux, Gene Y. Im, Joan Saldarriaga, Thierry Gustot, Jacques Devière, Swan N. Thung, Charlotte Minsart, Thomas Sersté, Gianluca Bontempi, Karim Abdelrahman, Jean Henrion, Delphine DegréValerio Lucidi, Laura Rubbia-Brandt, Venugopalan D. Nair, Christophe Moreno, Pierre Deltenre, Yujin Hoshida, Denis Franchimont

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background & Aims: Patients with severe alcoholic hepatitis (AH) have a high risk of death within 90 days. Corticosteroids, which can cause severe adverse events, are the only treatment that increases short-term survival. It is a challenge to predict outcomes of patients with severe AH. Therefore, we developed a scoring system to predict patient survival, integrating baseline molecular and clinical variables. Methods: We obtained fixed liver biopsy samples from 71 consecutive patients diagnosed with severe AH and treated with corticosteroids from July 2006 through December 2013 in Brussels, Belgium (derivation cohort). Gene expression patterns were analyzed by microarrays and clinical data were collected for 180 days. We identified gene expression signatures and clinical data that are associated with survival without liver transplantation at 90 and 180 days after initiation of corticosteroid therapy. Findings were validated using liver biopsies from 48 consecutive patients with severe AH treated with corticosteroids, collected from March 2010 through February 2015 at hospitals in Belgium and Switzerland (validation cohort 1) and in liver biopsies from 20 patients (9 received corticosteroid treatment), collected from January 2012 through May 2015 in the United States (validation cohort 2). Results: We integrated data on expression patterns of 123 genes and the model for end-stage liver disease (MELD) scores to assign patients to groups with poor survival (29% survived 90 days and 26% survived 180 days) and good survival (76% survived 90 days and 65% survived 180 days) (P <.001) in the derivation cohort. We named this assignment system the gene signature–MELD (gs-MELD) score. In validation cohort 1, the gs-MELD score discriminated patients with poor survival (43% survived 90 days) from those with good survival (96% survived 90 days) (P <.001). The gs-MELD score also discriminated between patients with a poor survival at 180 days (34% survived) and a good survival at 180 days (84% survived) (P <.001). The time-dependent area under the receiver operator characteristic curve for the score was 0.86 (95% confidence interval 0.73–0.99) for survival at 90 days, and 0.83 (95% confidence interval 0.71–0.96) for survival at 180 days. This score outperformed other clinical models to predict survival of patients with severe AH in validation cohort 1. In validation cohort 2, the gs-MELD discriminated patients with a poor survival at 90 days (12% survived) from those with a good survival at 90 days (100%) (P <.001). Conclusions: We integrated data on baseline liver gene expression pattern and the MELD score to create the gs-MELD scoring system, which identifies patients with severe AH, treated or not with corticosteroids, most and least likely to survive for 90 and 180 days.

Original languageEnglish (US)
Pages (from-to)965-975
Number of pages11
JournalGastroenterology
Volume154
Issue number4
DOIs
StatePublished - Mar 2018
Externally publishedYes

Fingerprint

Alcoholic Hepatitis
End Stage Liver Disease
Transcriptome
Survival
Adrenal Cortex Hormones
Genes
Liver
Belgium
Biopsy
Confidence Intervals
Gene Expression
Switzerland

Keywords

  • Cirrhosis
  • Ethanol
  • MELD
  • Transcription

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Combination of Gene Expression Signature and Model for End-Stage Liver Disease Score Predicts Survival of Patients With Severe Alcoholic Hepatitis. / Trépo, Eric; Goossens, Nicolas; Fujiwara, Naoto; Song, Won Min; Colaprico, Antonio; Marot, Astrid; Spahr, Laurent; Demetter, Pieter; Sempoux, Christine; Im, Gene Y.; Saldarriaga, Joan; Gustot, Thierry; Devière, Jacques; Thung, Swan N.; Minsart, Charlotte; Sersté, Thomas; Bontempi, Gianluca; Abdelrahman, Karim; Henrion, Jean; Degré, Delphine; Lucidi, Valerio; Rubbia-Brandt, Laura; Nair, Venugopalan D.; Moreno, Christophe; Deltenre, Pierre; Hoshida, Yujin; Franchimont, Denis.

In: Gastroenterology, Vol. 154, No. 4, 03.2018, p. 965-975.

Research output: Contribution to journalArticle

Trépo, E, Goossens, N, Fujiwara, N, Song, WM, Colaprico, A, Marot, A, Spahr, L, Demetter, P, Sempoux, C, Im, GY, Saldarriaga, J, Gustot, T, Devière, J, Thung, SN, Minsart, C, Sersté, T, Bontempi, G, Abdelrahman, K, Henrion, J, Degré, D, Lucidi, V, Rubbia-Brandt, L, Nair, VD, Moreno, C, Deltenre, P, Hoshida, Y & Franchimont, D 2018, 'Combination of Gene Expression Signature and Model for End-Stage Liver Disease Score Predicts Survival of Patients With Severe Alcoholic Hepatitis', Gastroenterology, vol. 154, no. 4, pp. 965-975. https://doi.org/10.1053/j.gastro.2017.10.048
Trépo, Eric ; Goossens, Nicolas ; Fujiwara, Naoto ; Song, Won Min ; Colaprico, Antonio ; Marot, Astrid ; Spahr, Laurent ; Demetter, Pieter ; Sempoux, Christine ; Im, Gene Y. ; Saldarriaga, Joan ; Gustot, Thierry ; Devière, Jacques ; Thung, Swan N. ; Minsart, Charlotte ; Sersté, Thomas ; Bontempi, Gianluca ; Abdelrahman, Karim ; Henrion, Jean ; Degré, Delphine ; Lucidi, Valerio ; Rubbia-Brandt, Laura ; Nair, Venugopalan D. ; Moreno, Christophe ; Deltenre, Pierre ; Hoshida, Yujin ; Franchimont, Denis. / Combination of Gene Expression Signature and Model for End-Stage Liver Disease Score Predicts Survival of Patients With Severe Alcoholic Hepatitis. In: Gastroenterology. 2018 ; Vol. 154, No. 4. pp. 965-975.
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author = "Eric Tr{\'e}po and Nicolas Goossens and Naoto Fujiwara and Song, {Won Min} and Antonio Colaprico and Astrid Marot and Laurent Spahr and Pieter Demetter and Christine Sempoux and Im, {Gene Y.} and Joan Saldarriaga and Thierry Gustot and Jacques Devi{\`e}re and Thung, {Swan N.} and Charlotte Minsart and Thomas Serst{\'e} and Gianluca Bontempi and Karim Abdelrahman and Jean Henrion and Delphine Degr{\'e} and Valerio Lucidi and Laura Rubbia-Brandt and Nair, {Venugopalan D.} and Christophe Moreno and Pierre Deltenre and Yujin Hoshida and Denis Franchimont",
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language = "English (US)",
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pages = "965--975",
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TY - JOUR

T1 - Combination of Gene Expression Signature and Model for End-Stage Liver Disease Score Predicts Survival of Patients With Severe Alcoholic Hepatitis

AU - Trépo, Eric

AU - Goossens, Nicolas

AU - Fujiwara, Naoto

AU - Song, Won Min

AU - Colaprico, Antonio

AU - Marot, Astrid

AU - Spahr, Laurent

AU - Demetter, Pieter

AU - Sempoux, Christine

AU - Im, Gene Y.

AU - Saldarriaga, Joan

AU - Gustot, Thierry

AU - Devière, Jacques

AU - Thung, Swan N.

AU - Minsart, Charlotte

AU - Sersté, Thomas

AU - Bontempi, Gianluca

AU - Abdelrahman, Karim

AU - Henrion, Jean

AU - Degré, Delphine

AU - Lucidi, Valerio

AU - Rubbia-Brandt, Laura

AU - Nair, Venugopalan D.

AU - Moreno, Christophe

AU - Deltenre, Pierre

AU - Hoshida, Yujin

AU - Franchimont, Denis

PY - 2018/3

Y1 - 2018/3

N2 - Background & Aims: Patients with severe alcoholic hepatitis (AH) have a high risk of death within 90 days. Corticosteroids, which can cause severe adverse events, are the only treatment that increases short-term survival. It is a challenge to predict outcomes of patients with severe AH. Therefore, we developed a scoring system to predict patient survival, integrating baseline molecular and clinical variables. Methods: We obtained fixed liver biopsy samples from 71 consecutive patients diagnosed with severe AH and treated with corticosteroids from July 2006 through December 2013 in Brussels, Belgium (derivation cohort). Gene expression patterns were analyzed by microarrays and clinical data were collected for 180 days. We identified gene expression signatures and clinical data that are associated with survival without liver transplantation at 90 and 180 days after initiation of corticosteroid therapy. Findings were validated using liver biopsies from 48 consecutive patients with severe AH treated with corticosteroids, collected from March 2010 through February 2015 at hospitals in Belgium and Switzerland (validation cohort 1) and in liver biopsies from 20 patients (9 received corticosteroid treatment), collected from January 2012 through May 2015 in the United States (validation cohort 2). Results: We integrated data on expression patterns of 123 genes and the model for end-stage liver disease (MELD) scores to assign patients to groups with poor survival (29% survived 90 days and 26% survived 180 days) and good survival (76% survived 90 days and 65% survived 180 days) (P <.001) in the derivation cohort. We named this assignment system the gene signature–MELD (gs-MELD) score. In validation cohort 1, the gs-MELD score discriminated patients with poor survival (43% survived 90 days) from those with good survival (96% survived 90 days) (P <.001). The gs-MELD score also discriminated between patients with a poor survival at 180 days (34% survived) and a good survival at 180 days (84% survived) (P <.001). The time-dependent area under the receiver operator characteristic curve for the score was 0.86 (95% confidence interval 0.73–0.99) for survival at 90 days, and 0.83 (95% confidence interval 0.71–0.96) for survival at 180 days. This score outperformed other clinical models to predict survival of patients with severe AH in validation cohort 1. In validation cohort 2, the gs-MELD discriminated patients with a poor survival at 90 days (12% survived) from those with a good survival at 90 days (100%) (P <.001). Conclusions: We integrated data on baseline liver gene expression pattern and the MELD score to create the gs-MELD scoring system, which identifies patients with severe AH, treated or not with corticosteroids, most and least likely to survive for 90 and 180 days.

AB - Background & Aims: Patients with severe alcoholic hepatitis (AH) have a high risk of death within 90 days. Corticosteroids, which can cause severe adverse events, are the only treatment that increases short-term survival. It is a challenge to predict outcomes of patients with severe AH. Therefore, we developed a scoring system to predict patient survival, integrating baseline molecular and clinical variables. Methods: We obtained fixed liver biopsy samples from 71 consecutive patients diagnosed with severe AH and treated with corticosteroids from July 2006 through December 2013 in Brussels, Belgium (derivation cohort). Gene expression patterns were analyzed by microarrays and clinical data were collected for 180 days. We identified gene expression signatures and clinical data that are associated with survival without liver transplantation at 90 and 180 days after initiation of corticosteroid therapy. Findings were validated using liver biopsies from 48 consecutive patients with severe AH treated with corticosteroids, collected from March 2010 through February 2015 at hospitals in Belgium and Switzerland (validation cohort 1) and in liver biopsies from 20 patients (9 received corticosteroid treatment), collected from January 2012 through May 2015 in the United States (validation cohort 2). Results: We integrated data on expression patterns of 123 genes and the model for end-stage liver disease (MELD) scores to assign patients to groups with poor survival (29% survived 90 days and 26% survived 180 days) and good survival (76% survived 90 days and 65% survived 180 days) (P <.001) in the derivation cohort. We named this assignment system the gene signature–MELD (gs-MELD) score. In validation cohort 1, the gs-MELD score discriminated patients with poor survival (43% survived 90 days) from those with good survival (96% survived 90 days) (P <.001). The gs-MELD score also discriminated between patients with a poor survival at 180 days (34% survived) and a good survival at 180 days (84% survived) (P <.001). The time-dependent area under the receiver operator characteristic curve for the score was 0.86 (95% confidence interval 0.73–0.99) for survival at 90 days, and 0.83 (95% confidence interval 0.71–0.96) for survival at 180 days. This score outperformed other clinical models to predict survival of patients with severe AH in validation cohort 1. In validation cohort 2, the gs-MELD discriminated patients with a poor survival at 90 days (12% survived) from those with a good survival at 90 days (100%) (P <.001). Conclusions: We integrated data on baseline liver gene expression pattern and the MELD score to create the gs-MELD scoring system, which identifies patients with severe AH, treated or not with corticosteroids, most and least likely to survive for 90 and 180 days.

KW - Cirrhosis

KW - Ethanol

KW - MELD

KW - Transcription

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