Fecal microbiota transplantation in severe alcohol-associated hepatitis: mortality effect and 3 PM-guided analysis of associated factors.
Notice bibliographique
Résumé
Abstract Background: Severe alcohol-associated hepatitis (SAH) is the most serious phenotype of the alcohol-associated liver disease (ALD) spectrum, characterized by high short-term mortality. The only approved therapy with corticosteroids (CS) has modest and short-term survival benefits; moreover, new therapeutic alternatives are unmet need. Fecal microbiota transplantation (FMT) has gained attention as a potential therapeutic option for filling this gap. In this study, we aimed to determine the effect of FMT on mortality in patients with SAH beyond CS and search for factors predictive of outcome, which could be leveraged in a real-life predictive, preventive, and personalized medicine (3 PM) management of SAH. Methods: We conducted a prospective study (NCT04758806) in adult patients with SAH, non-responders (NR) to CS, or non-eligible (NE) for CS between January 2018 and August 2022. FMT intervention consisted of five 100 ml doses (prepared beforehand from 30g stool from an unrelated healthy donor and frozen at − 80°C) administered daily to the upper gastrointestinal (GI) tract. We evaluated the impact of FMT on short-term mortality as determined by the propensity score matching with the historical cohort derived from our RH7 registry (NCT04767945). Also, we scrutinized SAH-related prognostic factors and scores such as Model for end-stage liver disease (MELD), Maddrey Discriminant Function (MDF), Acute-on-chronic liver failure (ACLF), Liver Frailty Index (LFI), Hepatic venous-portal gradient (HVPG) and AAHS (Alcoholic Hepatitis Histologic Score), for more precise prediction of response to therapy and their future potential in predictive, preventive, and personalized patient management. Results: We enrolled 44 patients with SAH (NR + NE to CS) who were intended to be treated with FMT and analyzed 33 patients per protocol (after an additional 11 being excluded for receiving less than 5 doses of FMT). The mean age was 49.6y, 11 patients (33.3%) were females. The median MELD-Na score was 29, and ACLF of any degree had 27 patients (81.8%). FMT improved 30-day survival over the historical control group (p = 0.0204); ninety-day survival was improved but did not reach statistical significance (p = 0.4386). As predictors of FMT failure - evaluated by the surrogate of short-term mortality -, we identified baseline MELD ≥30, MDR ≥ 90, and ACLF grade > 1, respectively (p=0.016; p=0.024; p=0.01). Survival was not associated with baseline liver frailty index (LFI), hepatic venous-portal gradient (HVPG), or Alcoholic Hepatitis Histological Score (AHHS). Conclusion: Severe alcohol-associated hepatitis in patients beyond CS was confirmed to be associated with high short-term mortality. In this difficult-to-treat cohort, FMT improved 30-day survival over historical controls chosen by propensity score matching. Factors associated with better outcomes were MELD-Na ≤ 30, MDR ≤ 90, and ACLF < 2. Therefore, our results lend support to the notion that FMT can be considered a 3 PM approach: albeit more data is needed, FMT and the described factors are good candidates for the unmet need of preventing death, predicting therapeutic response, and personalized management of SAH.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».