Dataset Information

Gene signature-MELD score and alcohol relapse determine long-term prognosis of patients with severe alcoholic hepatitis.

ABSTRACT:

Background

The gene-signature-model for end stage liver disease (gs-MELD) score has been shown to be a strong predictor of 6-month survival in severe alcoholic hepatitis (AH). Currently, only a few studies have evaluated the long-term prognosis of patients with severe AH.

Aim

To assess the prognostic value of the gs-MELD score at 5 years in patients with severe AH.

Methods

Forty-eight consecutive patients with AH (25 males, median age 52 years [95% IC: 48-56]) were included.

Results

The median gs-MELD score was 2.6 (95% CI: 2.2-3.0). According to the gs-MELD score, 22 patients (46%) were considered to have a poor prognosis. During a median follow-up of 29 months (95% CI: 4-43), 19 patients (40%) were abstinent and 24 patients (50%) died. At 5 years, rates of survival were 61% (95% CI: 41-81) and 26% (95% CI: 11-55) in patients with low and high gs-MELD scores (P = .001), and 81% (95% CI: 58-96) and 22% (95% CI: 10-47) in abstainers and in consumers (P < .001) respectively. In multivariable competing risk regression modelling, gs-MELD score (subdistribution hazard ratio: 5.78, 95% CI: 2.17-15.38, P < .001) and recurrent alcohol consumption (subdistribution hazard ratio: 12.18, 95% CI: 3.16-46.95, P < .001) were independently associated with 5-year mortality.

Conclusions

Both gs-MELD score and alcohol consumption drive AH long-term prognosis. The gs-MELD score may guide the development of molecularly targeted therapies in AH.

SUBMITTER: Deltenre P

PROVIDER: S-EPMC7056530 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

Gene signature-MELD score and alcohol relapse determine long-term prognosis of patients with severe alcoholic hepatitis.

Deltenre Pierre P Trépo Eric E Fujiwara Naoto N Goossens Nicolas N Marot Astrid A Dubois Margaux M Spahr Laurent L Henrion Jean J Moreno Christophe C Hoshida Yujin Y

Liver international : official journal of the International Association for the Study of the Liver 20191015 3

<h4>Background</h4>The gene-signature-model for end stage liver disease (gs-MELD) score has been shown to be a strong predictor of 6-month survival in severe alcoholic hepatitis (AH). Currently, only a few studies have evaluated the long-term prognosis of patients with severe AH.<h4>Aim</h4>To assess the prognostic value of the gs-MELD score at 5 years in patients with severe AH.<h4>Methods</h4>Forty-eight consecutive patients with AH (25 males, median age 52 years [95% IC: 48-56]) were included ...[more]

PMID: 31568650

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Project description:Importance: Severe alcoholic hepatitis (AH) is a highly lethal disease with a 3-month mortality up to 50%. Corticosteroids are the current standard of care although nearly 40% of the patients do not respond and accurate pre-treatment predictors of survival are lacking. Objective: To develop a prognostic score based on molecular and clinical variables before initiation of corticosteroids. Design, Setting, and Participants: Gene expression profiling of fixed liver biopsy obtained for diagnosis of severe AH assessed in 3 independent cohorts (1 prospective cohort for prognostic gene signature and integrative score derivation, and 2 retrospective cohorts for validation). Samples were obtained from 4 European and 1 US medical centers between July 2006 and February 2015. Exposures: Biopsy proven severe AH patients treated with corticosteroids. Main Outcome Measures: Identification of a gene signature combined with a validated clinical index to develop an integrative prognostic score of survival without death or liver transplantation in a derivation cohort (n=71). Prognostic performance of the score was validated in an independent multi-center validation cohort 1 (n=48). Finally, the score was implemented in an FDA-approved clinical diagnostic platform (NanoString) and tested in another independent validation cohort 2 (n=20). Results: A prognostic score, integrating a 123-gene signature and the model for end-stage liver disease (gs-MELD score), was defined in the derivation cohort, in which poor- and good-prognosis patients were discriminated with a cut-off value of 2.66 at 3 months (event-free survival rates of 32% vs. 76%, respectively, p<.001) and 6 months (26% vs. 65%, respectively, p<.001). In the validation cohort 1, the score similarly discriminated poor- and good-prognosis patients at 3 months (43%, [95% CI, 26%-70%] vs. 96% [95% CI, 89%-100%], respectively, p<.001, c-index of 0.83 [95% CI, 0.66-0.99]) and 6 months (34% [95% CI, 18%-61%] vs 84% [95% CI, 72%-100%], respectively, p<.001, c-index of 0.80 [95% CI, 0.66-0.94]), and outperformed other existing clinical indices. The NanoString-based gs-MELD score remained predictive of 3- (p=.03) and 6-month (p=.009) even-free survival in the validation cohort 2. Conclusion and Relevance: The gs-MELD score, incorporating clinically applicable gene signature test and the MELD score, enables pre-treatment survival prediction in severe AH patients.

Dataset Information

Gene signature-MELD score and alcohol relapse determine long-term prognosis of patients with severe alcoholic hepatitis.

Background

Aim

Methods

Results

Conclusions

Publications

Gene signature-MELD score and alcohol relapse determine long-term prognosis of patients with severe alcoholic hepatitis.

Similar Datasets

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