Bibliographic record
Abstract
Background: Alcoholic hepatitis (AH) results from hepatic inflammation, oxidative damage, cholestasis and apoptosis, all of which induce a vicious cycle that leads to liver and secondary organ failure associated with poor prognosis.Study Design: Vital Therapies' study VTI-208 was conducted in subjects with AH, using an extracorporeal hepatocellular therapy system (ELAD) containing human C3A hepatoma cells, to determine if ELAD can increase survival in AH.C3A cells express acute phase response and immune-modulatory proteins and growth factors and may provide anti-inflammatory therapy and support hepatocellular function in early stages of AH.Inclusion/Exclusion Criteria: Subjects >18yrs old with a clinical or histologic diagnosis of AH, bilirubin >8mg/dl, Maddrey DF >32, MELD ≤35, platelets ≥40,000, and without severe concomitant disease, uncontrolled sepsis or bleeding, hemodynamic instability or need for chronic dialysis.Intervention: Subjects were randomized to either 3-5 days continuous ELAD therapy plus standard of care (SOC) or to SOC alone.Endpoint: Overall survival (OS) assessed by Kaplan-Meier analysis.Pre-specified subgroups included subjects with MELD and age >/< baseline median.Results: From 2013-2015, 203 subjects were enrolled (96 ELAD and 107 SOC), at 40 sites worldwide.Comparison of baseline characteristics showed no significant differences between groups and within subgroups, including treatment with steroids or pentoxifylline.There was no significant difference in serious adverse events between groups and no unexpected serious adverse events were related to the cellular component.In an intent-to-treat (ITT) analysis, there was no significant difference in OS (52.1% vs 52.3%).Subgroup analysis showed strong trends toward improved OS in groups in which MELD or age were lower than baseline medians.The majority of subjects (n=120) presented with MELD <28 and in this group, ELAD was associated with a trend toward higher OS (71% vs 57%, p=0.077).A similar trend was seen in younger subjects (n=101) (67% vs 55%, p=0.167).Although not pre-specified, survival in subjects with a combination of MELD and age less than baseline median (n=59) was significantly better in ELAD than SOC (100% vs 73%, p=0.006) at 91 days.After 100 days, survival was fairly stable in all subject groups.Conclusion: There was no difference in OS between ELAD and SOC but there was a trend toward survival benefit in patients with MELD <28 or age <47 years.These data suggest ELAD may be a favorable AH treatment modality in younger patients with sufficient renal function and less severe coagulopathy.A study to confirm the survival benefit in this population is in preparation and is scheduled to start in 2016.
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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 | 0.002 | 0.013 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.003 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.008 | 0.003 |
| Open science | 0.002 | 0.004 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.809 | 0.692 |
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".