Understanding acute kidney injury (AKI) in liver cirrhosis from the acute-on-chronic liver failure (ACLF) perspective
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PROVIDER: S-EPMC11336529 | biostudies-literature | 2024 Jul
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND In the intensive care unit (ICU), critically ill patients with cirrhosis and acute-on-chronic liver failure (ACLF) continue to have high mortality rates. The AARC ACLF score is a simple, newly-developed score based on Asian ACLF patients, which performs well in prognosis. The present study attempted to verify the prognostic ability of AARC ACLF in non-Asian critically ill patients with cirrhosis and ACLF. MATERIAL AND METHODS We enrolled 786 patients. Relevant clinical data were collected within 24 h after admission to compare the differences between survivors and non-survivors, and all the patients were followed up for at least 180 days. RESULTS The 28-day, 90-day, and 180-day mortality rates were 28.9% (227/786), 36.4% (286/786), and 40.3% (317/786), respectively. Multivariate Cox regression analysis showed that AARC ACLF score (HR: 1.375, 95% CI: 1.247-1.516, P<0.001) was an independent predictive factor of 28-day mortality, and the AUROC of the predictive ability in 28-day mortality of the AARC ACLF score was 0.754. In addition, the AARC ACLF score was regraded into 3 classes (low risk: AARC ACLF <9, intermediate risk: 9≤ AARC ACLF <12, and high risk: AARC ACLF ≥12). The AARC ACLF score can be used for dynamic assessment by retest at days 4-7. CONCLUSIONS The AARC ACLF score has a good predictive value for 28-day, 90-day, and 180-day mortality in non-Asian critically ill patients with cirrhosis and ACLF, which is not inferior to CLIF-C ACLFsLact and other models. It is easy to use at bedside, and it is dynamic and reliable.
| S-EPMC7526342 | biostudies-literature
Project description:Psoralea corylifolia Linn (Bakuchi or Babchi), commonly known as purple fleabane, is a popular herb used in Ayurvedic traditional medicine. Its seeds, called Fructus Psoraleae, are traditionally used for treating leprosy, vitiligo, and psoriasis in the absence of empirical evidence. We report the first case of acute on chronic liver failure (ACLF) caused by Bakuchi, a well-documented hepatotoxic agent, in a middle-aged female. Her liver function deteriorated progressively which prompted us to go for a liver biopsy which was consistent with diagnosis of herb-induced liver injury after excluding all competing causes. Fortunately, the patient improved gradually after herb withdrawal and supportive care. Patients with underlying chronic liver disease (CLD) should be aware of risks in using untested herbal formulations. This case emphasizes the need for increased surveillance to formulate guidelines regarding the regulation and informed use of herbal supplements in patients with chronic liver disease.
| S-EPMC10709202 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-02-24 | GSE142256 | GEO
Project description:Neutrophils were isolated (using Ficoll, Dextran and water to lyse the red cells) from whole blood of 5 healthy subjects, 5 patients with stable cirrhosis and 5 patients with ACLF. RNA was then extracted and amplified 100 ng of RNA per sample were then hybridized on ClarionS array (Affymetrix, Thermofischer scientific)
2021-02-24 | GSE142254 | GEO
Project description:BackgroundPatients with cirrhosis and ascites (and portal hypertension) are at risk of developing acute kidney injury (AKI). Although many etiologies exist, hepatorenal AKI (HRS-AKI) remains a frequent and difficult-to-treat cause, with a very high mortality when left untreated. The standard of care is the use of terlipressin and albumin. This can lead to reversal of AKI, which is associated to survival. Nevertheless, only approximately half of the patients achieve this reversal and even after reversal patients remains at risk for new episodes of HRS-AKI. TIPS is accepted for use in patients with variceal bleeding and refractory ascites, which leads to a reduction in portal pressure. Although preliminary data suggest it may be useful in HRS-AKI, its use in this setting is controversial and caution is recommended given the fact that HRS-AKI is associated to cardiac alterations and acute-on-chronic liver failure (ACLF) which represent relative contraindications for transjugular intrahepatic portosystemic shunt (TIPS). In the last decades, with the new definition of renal failure in patients with cirrhosis, patients are identified at an earlier stage. These patients are less sick and therefore more likely to not have contraindications for TIPS. We hypothesize that TIPS could be superior to the standard of care in patients with HRS-AKI.MethodsThis study is a prospective, multicenter, open, 1:1-randomized, controlled parallel-group trial. The main end-point is to compare the 12-month liver transplant-free survival in patients assigned to TIPS compared to the standard of care (terlipressin and albumin). Secondary end-point include reversal of HRS-AKI, health-related Quality of Life (HrQoL), and incidence of further decompensation among others. Once patients are diagnosed with HRS-AKI, they will be randomized to TIPS or Standard of Care (SOC). TIPS should be placed within 72 h. Until TIPS placement, TIPS patients will be treated with terlipressin and albumin. Once TIPS is placed, terlipressin and albumin should be weaned off according to the attending physician.DiscussionIf the trial were to show a survival advantage for patients who undergo TIPS placement, this could be incorporated in routine clinical practice in the management of patients with HRS-AKI.Trial registrationClinicaltrials.gov NCT05346393 . Released to the public on 01 April 2022.
| S-EPMC10077612 | biostudies-literature
Project description:Terlipressin with albumin, the recommended treatment for hepatorenal syndrome-acute kidney injury (HRS-AKI), is associated with adverse events. Furthermore, the course of AKI in patients with acute-on-chronic liver failure (ACLF) is unknown. We aimed to analyze the safety and efficacy of terlipressin infusion and AKI course in patients with ACLF. We prospectively enrolled consecutive adult patients with ACLF with HRS-AKI (satisfying EASL criteria) treated with terlipressin infusion between 14 October 2019 and 24 July 2020. The objectives were to assess the incidence of adverse events, response to terlipressin, course of HRS-AKI and predictors of mortality. A total of 116 patients were included. Twenty-one percent of patients developed adverse effects. Only 1/3rd of patients who developed adverse events were alive at day 90. Sixty-five percent of the patients responded to terlipressin. Nearly 22% developed recurrence of HRS, and 5.2% progressed to HRS-chronic kidney disease. TFS was 70.4% at day 30 and 57.8% at day 90. On multivariate stepwise Cox regression analysis terlipressin non-response (hazard ratio [HR], 3.49 [1.85-6.57]; P < 0.001) and MELD NA score (HR,1.12 [1.06-1.18]; P < 0.001) predicted mortality at day-90. Patients with ACLF who develop terlipressin related adverse events have dismal prognoses. Terlipressin non-response predicts mortality in patients with ACLF and HRS-AKI.
| S-EPMC8976022 | biostudies-literature
Project description:Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the "APASL ACLF Research Consortium (AARC)" was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia-Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the 'Golden Therapeutic Window', the 'transplant window', and plasmapheresis as a treatment modality. Also, the data has been key to identifying pediatric ACLF. The European Association for the Study of Liver-Chronic Liver Failure (EASL CLIF) and the North American Association for the Study of the End Stage Liver Disease (NACSELD) from the West added the concepts of organ failure and infection as precipitants for the development of ACLF and CLIF-Sequential Organ Failure Assessment (SOFA) and NACSELD scores for prognostication. The Chinese Group on the Study of Severe Hepatitis B (COSSH) added COSSH-ACLF criteria to manage hepatitis b virus-ACLF with and without cirrhosis. The literature supports these definitions to be equally effective in their respective cohorts in identifying patients with high mortality. To overcome the differences and to develop a global consensus, APASL took the initiative and invited the global stakeholders, including opinion leaders from Asia, EASL and AASLD, and other researchers in the field of ACLF to identify the key issues and develop an evidence-based consensus document. The consensus document was presented in a hybrid format at the APASL annual meeting in Kyoto in March 2024. The 'Kyoto APASL Consensus' presented below carries the final recommendations along with the relevant background information and areas requiring future studies.
| S-EPMC11846769 | biostudies-literature
Project description:Acute kidney injury (AKI) currently is diagnosed by a temporal trend of a single blood analyte: serum creatinine. This measurement is neither sensitive nor specific to kidney injury or its protean forms. Newer biomarkers, neutrophil gelatinase-associated lipocalin (NGAL, Lipocalin 2, Siderocalin), or kidney injury molecule-1 (KIM-1, Hepatitis A Virus Cellular Receptor 1), accelerate the diagnosis of AKI as well as prospectively distinguish rapidly reversible from prolonged causes of serum creatinine increase. Nonetheless, these biomarkers lack the capacity to subfractionate AKI further (eg, sepsis versus ischemia versus nephrotoxicity from medications, enzymes, or metals) or inform us about the primary and secondary sites of injury. It also is unknown whether all nephrons are injured in AKI, whether all cells in a nephron are affected, and whether injury responses can be stimulus-specific or cell type-specific or both. In this review, we summarize fully agnostic tissue interrogation approaches that may help to redefine AKI in cellular and molecular terms, including single-cell and single-nuclei RNA sequencing technology. These approaches will empower a shift in the current paradigm of AKI diagnosis, classification, and staging, and provide the renal community with a significant advance toward precision medicine in the analysis AKI.
| S-EPMC5753434 | biostudies-literature
Project description:Acute-on-chronic liver failure (ACLF) is a syndrome that develops in patients with acutely decompensated chronic liver disease. It is characterised by high 28-day mortality, the presence of one or more organ failures (OFs) and a variable but severe grade of systemic inflammation. Despite the peculiarity of each one, every definition proposed for ACLF recognizes it as a proper clinical entity. In this paper, we provide an overview of the diagnostic criteria proposed by the different scientific societies and the clinical characteristics of the syndrome. Established and experimental treatments are also described. Among the former, the most relevant are directed to support organ failures, treat precipitating factors and carry out early assessment for liver transplantation (LT). Further studies are needed to better clarify pathophysiology of the syndrome and discover new therapies.
| S-EPMC8509281 | biostudies-literature
Project description:Renal hypoxia is widespread in acute kidney injury (AKI) of various aetiologies. Hypoxia adaptation, conferred through the hypoxia-inducible factor (HIF), appears to be insufficient. Here we show that HIF activation in renal tubules through Pax8-rtTA-based inducible knockout of von Hippel-Lindau protein (VHL-KO) protects from rhabdomyolysis-induced AKI. In this model, histological observations indicate that injury mainly affects proximal convoluted tubules, with 5% necrosis at d1 and 40% necrosis at d2. HIF-1alpha up-regulation in distal tubules reflects renal hypoxia. However, lack of HIF in proximal tubules suggests insufficient adaptation by HIF. AKI in VHL-KO mice leads to prominent HIF activation in all nephron segments, as well as to reduced serum creatinine, serum urea, tubular necrosis, and apoptosis marker caspase-3 protein. At d1 after rhabdomyolysis, when tubular injury is potentially reversible, HIF mediated protection in AKI is associated with activated glycolysis, cellular glucose uptake and utilization, autophagy, vasodilation, and proton removal as demonstrated by qPCR, pathway enrichment analysis and immunohistochemistry. Together, our data provide evidence for a HIF-orchestrated multi-level shift towards glycolysis as a major mechanism for protection against acute tubular injury. All experiments were carried out in transgenic mice in which selective renal tubular VHL knockout (VHL-KO) was inducible by doxycycline (Reference: Mathia S, Paliege A, Koesters R, Peters H, Neumayer HH, Bachmann S, Rosenberger C. Action of hypoxia-inducible factor in liver and kidney from mice with Pax8-rtTA-based deletion of von Hippel-Lindau protein. Acta Physiol (Oxf). 2013; 207(3):565-76.). Four groups of animals were used: 1) controls: untreated mice; 2) VHL-KO: injected with doxycycline (0.1 mg per 10 g body weight SC), 4 days prior to sacrifice; 3) AKI: rhabdomyolysis; 4) VHL-KO/AKI: doxycycline plus rhabdomyolysis. To induce AKI, 50% glycerol (0.05 ml per 10 g body weight) was injected IM into the left hind limb under isoflurane narcosis. Drinking water was withdrawn between 20 h prior and 24 h after glycerol injection.
2013-09-05 | E-GEOD-44925 | biostudies-arrayexpress