SuO015VS-01 - A PROMISING INTRAPERITONEAL TREATMENT TO MANAGE HEPATIC ENCEPHALOPATHY AND RENAL FAILURE IN CIRRHOTIC PATIENTS
Bibliographic record
Abstract
INTRODUCTION AND AIMS: Renal insufficiency is one of the most common and life-threatening complications of decompensated liver cirrhosis. A deterioration of the liver and kidney functions leads to metabolic imbalances that can in turn trigger other organ failures. In particular, it is often associated with hyperammonemia, the main culprit of hepatic encephalopathy (HE) potentially leading to brain failure. This syndrome called acute-on-chronic liver failure (ACLF) is associated with a high short-term mortality of 85%. The current standard of care relies on treating the precipitating factor responsible for the liver decompensation and on supportive care. Hemodialysis is routinely used in kidney-impaired patients, but can lead to hemodynamic instability. Peritoneal dialysis (PD) is emerging as the treatment of choice for patients with liver cirrhosis and end stage renal failure, but it is limited in ammonia removal which is crucial to guarantee the survival of patients with HE. METHODS: A pH-gradient liposomes suspension (VS-01) was designed for intraperitoneal infusion to enhance the clearance of ammonia and other liver and uremic toxins known to accumulate in ACLF patients. During a 3-hour dwell time, the instilled liposomes remain in the peritoneal cavity and continuously extract ammonia from the body by scavenging it into their core. Simultaneously, liver and uremic toxins are cleared by passive diffusion based on PD principles. At the end of the treatment, these vesicles and their toxic cargo are drained out of the patient. RESULTS: VS-01 is currently under preclinical development. In a rat model of secondary cirrhosis induced by bile duct ligation, VS-01 demonstrated a fast and efficient removal of ammonia, 10-fold superior to a control PD, significantly reducing the plasmatic ammonia levels and attenuating the associated brain edema. The safety of VS-01 was investigated in rats and pigs. The latter is a gold-standard model to study colloids-related hypersensitive immune reactions. The results show that VS-01 is well tolerated and does not induce any pseudoallergic reactions related to complement activation. CONCLUSIONS: These findings highlight the clinical potential of VS-01 to rapidly remove ammonia. This new, potentially lifesaving therapy for the prompt management of HE and simultaneous support of kidney and liver functions will now be investigated in clinical studies in patients with ACLF. Funding from the Swiss Commission for Technology and Innovation is acknowledged.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.003 | 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".