Fecal microbiota transplantation in severe alcohol-associated hepatitis: mortality effect and 3 PM-guided analysis of associated factors.
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".