ArticleNature medicine2014
Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin E2.
Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
143 citing papers in PubMed, 2 syntheses or guidelines pooled it, 283 citations in OpenAlex.
- Use of human albumin infusion in cirrhotic patients: a systematic review and meta-analysis of randomized controlled trials.Hepatology international · 2022Pooled it
- Effectiveness of influenza vaccines in adults with chronic liver disease: a systematic review and meta-analysis.BMJ open · 2019Pooled it
- Albumin Replacement Therapy in Septic Shock: A Randomized Clinical Trial.JAMA network open · 2026Trial
- Targeted Albumin Infusions Do Not Improve Systemic Inflammation or Cardiovascular Function in Decompensated Cirrhosis.Clinical and translational gastroenterology · 2022Trial
- Dysregulated Adaptive Immunity Is an Early Event in Liver Cirrhosis Preceding Acute-on-Chronic Liver Failure.Frontiers in immunology · 2020Trial
- Potent Anti-Inflammatory and Pro-Resolving Effects of Anabasum in a Human Model of Self-Resolving Acute Inflammation.Clinical pharmacology and therapeutics · 2018Trial
- ATTIRE: Albumin To prevenT Infection in chronic liveR failurE: study protocol for a single-arm feasibility trial.BMJ open · 2016Trial
- Uncovering immune dysfunction in ACLF: Cellular mechanisms, molecular pathways, and therapeutic frontiers.Journal of hepatology · 2026Review
- Acute-on-chronic liver failure and immune dysregulation: Systemic inflammation and immunoparesis paradox.Hepatology communications · 2026Review
- Advancements in Understanding the Role of Oxylipins in Liver Injury and Liver Failure.Journal of clinical and translational hepatology · 2026Review
- Preoperative serum albumin level is associated with postoperative short- and long-term renal function deterioration in patients who underwent radical cystectomy for bladder cancer.Investigative and clinical urology · 2026Article
- Early serum albumin dynamics in sepsis differ by albumin source and have implications for nutritional assessment.Frontiers in nutrition · 2026Article
- The Role of the Microbiome in the Resolution of Infection-Induced Inflammation.ACS infectious diseases · 2025Review
- Review
- Geriatric Nutritional Risk Index as a Predictor of Overall Survival in Cirrhosis: A Retrospective Cohort Study.Current medical science · 2025Article
- Ascites complications risk factors of decompensated cirrhosis patients: logistic regression and prediction model.BMC gastroenterology · 2025Article
- Immunological Mechanisms and Effects of Bacterial Infections in Acute-on-Chronic Liver Failure.Cells · 2025Review
- iSTAND trial of IVIG in POTS: a step in the right direction, but more studies are needed.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2025Article
- Potential therapies for acute-on-chronic liver failure.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Acute and non-acute decompensation of liver cirrhosis.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
83 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
Liver disease is one of the leading causes of death worldwide. Patients with cirrhosis display an increased predisposition to and mortality from infection due to multimodal defects in the innate immune system; however, the causative mechanism has remained elusive. We present evidence that the cyclooxygenase (COX)-derived eicosanoid prostaglandin E2 (PGE2) drives cirrhosis-associated immunosuppression. We observed elevated circulating concentrations (more than seven times as high as in healthy volunteers) of PGE2 in patients with acute decompensation of cirrhosis. Plasma from these and patients with end-stage liver disease (ESLD) suppressed macrophage proinflammatory cytokine secretion and bacterial killing in vitro in a PGE2-dependent manner via the prostanoid type E receptor-2 (EP2), effects not seen with plasma from patients with stable cirrhosis (Child-Pugh score grade A). Albumin, which reduces PGE2 bioavailability, was decreased in the serum of patients with acute decompensation or ESLD (<30 mg/dl) and appears to have a role in modulating PGE2-mediated immune dysfunction. In vivo administration of human albumin solution to these patients significantly improved the plasma-induced impairment of macrophage proinflammatory cytokine production in vitro. Two mouse models of liver injury (bile duct ligation and carbon tetrachloride) also exhibited elevated PGE2, reduced circulating albumin concentrations and EP2-mediated immunosuppression. Treatment with COX inhibitors or albumin restored immune competence and survival following infection with group B Streptococcus. Taken together, human albumin solution infusions may be used to reduce circulating PGE2 levels, attenuating immune suppression and reducing the risk of infection in patients with acutely decompensated cirrhosis or ESLD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.