Impact of long-term continuous terlipressin infusion on the renin-angiotensin-aldosterone system in patients with decompensated cirrhosis
Bibliographic record
Abstract
Background and aims Pooling of blood in the splanchnic circulation due to cirrhotic portal hypertension reduces effective circulating blood volume and activates the renin-angiotensin-aldosterone system (RAAS). This study investigates the effects of long-term continuous terlipressin infusion (CTI) on the RAAS in patients with decompensated cirrhosis. Methods 30 participants with cirrhosis and ascites were enrolled in a prospective crossover study comparing 12 weeks of home CTI to observation. Analysis of plasma renin concentration, aldosterone, ACE and ACE2 activity was performed. Results The median age of participants was 62 years (IQR 57–64), median model for end-stage liver disease-Na was 16 (12.3–20.8) and 73% (n=22) were male. Plasma renin decreased by a mean adjusted difference (MAD) of 479.25 mIU/L (95% CI −652.11 to –313.18, p<0.0001), and aldosterone decreased by a MAD of 698.26 pmol/L (95% CI −1009.28 to –396.30, p<0.0001) on CTI compared with observation. Serum ACE2 activity significantly increased by a MAD of 13.71 pmol/mL/min (95% CI 5.88 to 21.92, p=0.001) on CTI compared with observation, and ACE/ACE2 ratio decreased by a MAD of −0.34 (95% CI −0.52 to –0.17, p<0.0002). Conclusion This study demonstrates for the first time a significant attenuation of the classical RAAS and increase in ACE2 activity in patients with decompensated cirrhosis treated with long-term CTI, confirming the physiological mechanism of action of terlipressin in improving ascites and renal function in these patients. Further studies are required to explore the effect of CTI on the alternate RAAS and to determine whether long-term CTI can modulate the clinical progression of decompensated cirrhosis and prevent the development of complications including hepatorenal syndrome. Trial registration number ACTRN12619000891123.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".