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Open accessJournal ArticleDOI: 10.1056/NEJMOA2022166

A Randomized Trial of Albumin Infusions in Hospitalized Patients with Cirrhosis.

04 Mar 2021-The New England Journal of Medicine (Massachusetts Medical Society)-Vol. 384, Iss: 9, pp 808-817
Abstract: Background Infection and increased systemic inflammation cause organ dysfunction and death in patients with decompensated cirrhosis. Preclinical studies provide support for an antiinflamma...

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Topics: Organ dysfunction (59%), Cirrhosis (53%), Systemic inflammation (51%)
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32 results found


Open accessJournal ArticleDOI: 10.1093/GASTRO/GOAB040
Songtao Liu1, Qinghua Meng1, Yuan Xu2, Jianxin Zhou1Institutions (2)
Abstract: In cirrhosis with ascites, hepatorenal syndrome (HRS) is a specific prerenal dysfunction unresponsive to fluid volume expansion. Acute-on-chronic liver failure (ACLF) comprises a group of clinical syndromes with multiple organ failure and early high mortality. There are differences in the characterization of ACLF between the Eastern and Western medical communities. Patients with ACLF and acute kidney injury (AKI) have more structural injuries, contributing to confusion in diagnosing HRS-AKI. In this review, we discuss progress in the pathogenesis, diagnosis, and management of HRS-AKI, especially in patients with ACLF. Controversy regarding HRS-AKI in ACLF and acute liver failure, hepatic carcinoma, shock, sepsis, and chronic kidney disease is also discussed. Research on the treatment of HRS-AKI with ACLF needs to be more actively pursued to improve disease prognosis.

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3 Citations


Journal ArticleDOI: 10.1002/HEP.31836
01 Nov 2021-Hepatology
Abstract: Human serum albumin is the most abundant plasma protein, and it regulates diverse body functions. In patients with advanced and decompensated cirrhosis, serum albumin levels are low because of a reduction in the hepatocyte mass due to disease per se and multiple therapeutic interventions. Because of their oncotic and nononcotic properties, administration of human albumin solutions (HAS) have been found to be beneficial in patients undergoing large-volume paracentesis or who have hepatorenal syndrome or spontaneous bacterial peritonitis. Albumin also improves the functionality of the immune cells and mitigates the severity and risk of infections in advanced cirrhosis. Its long-term administration can modify the course of decompensated cirrhosis patients by reducing the onset of new complications, improving the quality of life, and probably providing survival benefits. There is, however, a need to rationalize the dose, duration, and frequency of albumin therapy in different liver diseases and stages of cirrhosis. In patients with acute-on-chronic liver failure, potentially toxic oxidized isoforms of albumin increase substantially, especially human nonmercaptalbumin and 2, and nitrosoalbumin. The role of administration of HAS in such patients is unclear. Determining whether removal of the pathological and dysfunctional albumin forms in these patients by "albumin dialysis" is helpful, requires additional studies. Use of albumin is not without adverse events. These mainly include allergic and transfusion reactions, volume overload, antibody formation and coagulation derangements. Considering their cost, limited availability, need for a health care setting for their administration, and potential adverse effects, judicious use of HAS in liver diseases is advocated. There is a need for new albumin molecules and economic alternatives in hepatologic practice.

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Topics: Serum albumin (67%), Hepatorenal syndrome (59%), Albumin (55%) ... read more

2 Citations


Open accessJournal ArticleDOI: 10.1111/LIV.15096
Abstract: Background & aims Guidelines recommend albumin as the plasma-expander of choice for acute kidney injury (AKI) in cirrhosis. However, the impact of these recommendations on patient outcomes remains unclear. We aimed to determine the practice-patterns and outcomes associated with albumin use in a large, nationwide-US cohort of hospitalized cirrhotics with AKI. Methods A retrospective cohort study was performed in hospitalized cirrhotics with AKI using Cerner-Health-Facts database from January 2009 to March 2018. 6786 were included for analysis on albumin-practice-patterns, and 4126 had available outcomes data. Propensity-score-adjusted model was used to determine the association between albumin use, AKI-recovery and in-hospital survival. Results Median age was 61-years (60% male, 70% white), median serum-creatinine was 1.8 mg/dL and median Model for End-stage Liver Disease Sodium (MELD-Na) score was 24. Albumin was given to 35% of patients, of which 50% received albumin within 48-hours of AKI-onset, and 17% received appropriate weight-based dosing. Albumin was used more frequently in patients with advanced complications of cirrhosis, higher MELD-Na scores and patients admitted to urban-teaching hospitals. After propensity-matching and multivariable adjustment, albumin use was not associated with AKI-recovery (odds ratio [OR] 0.70, 95% confidence-interval [CI]: 0.59-1.07, P = .130) or in-hospital survival (OR 0.76 [95% CI: 0.46-1.25], P = .280), compared with crystalloids. Findings were unchanged in subgroup analyses of patients with varying cirrhosis complications and disease severity. Conclusions USA hospitalized patients with cirrhosis and AKI frequently do not receive intravenous albumin, and albumin use was not associated with improved clinical outcomes. Prospective randomised trials are direly needed to evaluate the impact of albumin in cirrhotics with AKI.

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Topics: Retrospective cohort study (52%), Ascites (52%), Cirrhosis (51%) ... read more

1 Citations


Journal ArticleDOI: 10.1097/MNH.0000000000000730
Abstract: Purpose of review Hepatorenal syndrome (HRS) is encountered frequently in patients with end-stage liver disease and remains an important cause of morbidity and mortality in this patient population. This review will focus and provide updates on pathophysiology, assessment of kidney function, new definitions, and treatment and prevention of HRS. Recent findings Pathophysiology of HRS has been elucidated more recently and in addition to hemodynamic changes, the role of systemic inflammatory response contributes significantly to this process. Assessment of kidney function in patients with liver cirrhosis remains challenging. Novel glomerular filtration rate equations have been developed in patients with liver disease to better estimate kidney function and changes made in the definition of acute kidney injury (AKI), which are more aligned with KDIGO criteria for AKI. Vasoconstrictors, especially terlipressin, along with albumin remain the mainstay of pharmacological treatment of HRS-AKI. Biomarkers have been useful in differentiating ATN from HRS at an early stage. Summary HRS remains a significant cause of morbidity and mortality for patients with end-stage liver disease. Newer understanding of mechanisms in development and pathophysiology of HRS have helped with elucidation of the disease process.

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1 Citations


Open accessJournal ArticleDOI: 10.1159/000517363
Abstract: Objective assessment of fluid status is of utmost significance in the management of patients with complex disorders involving hemodynamics and multi-organ crosstalk such as cardiorenal or hepatorenal syndrome. The role of volume expansion using intravenous albumin in the setting of hepatorenal syndrome has been an everlasting debate among clinicians. With the accumulating evidence on the deleterious consequences of iatrogenic fluid overload, empiric albumin administration in these patients has been the focus of much attention, and the findings of recent studies suggest a higher incidence of pulmonary complications with albumin. Poor sensitivity of conventional physical examination has led to an interest in the utility of novel noninvasive bedside tools such as point-of-care ultrasonography (POCUS) to evaluate hemodynamics more precisely. Once confined to specialties such as obstetrics and emergency medicine, the scope of diagnostic POCUS is rapidly expanding in other fields including internal medicine and nephrology. Herein, we offer our perspective on the emerging role of POCUS for objective evaluation of patients with suspected hepatorenal physiology based on our experience. We propose that future clinical trials consider incorporating this strategy and explore the impact of POCUS-guided therapy on the outcomes.

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1 Citations


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23 results found


Journal ArticleDOI: 10.1002/HEP.1840080532
01 Sep 1988-Hepatology
Abstract: Renal sodium and water retention and plasma volume expansion have been shown to precede ascites formation in experimental cirrhosis. The classical "underfilling" theory, in which ascites formation causes hypovolemia and initiates secondary renal sodium and water retention, thus seems unlikely. While the occurrence of primary renal sodium and water retention and plasma volume expansion prior to ascites formation favors the "overflow" hypothesis, the stimulation of the renin-angiotensin-aldosterone system, vasopressin release and sympathetic nervous system associated with cirrhosis is not consonant with primary volume expansion. In this present article, the "Peripheral Arterial Vasodilation Hypothesis" is proposed as the initiator of sodium and water retention in cirrhosis. Peripheral arterial vasodilation is one of the earliest observations in the cirrhotic patient and experimental animals with cirrhosis. Arterial vasodilators and arteriovenous fistula are other examples in which renal sodium and water retention occur secondary to a decreased filling of the arterial vascular tree. An increase in cardiac output and hormonal stimulation are common features of cirrhosis, arteriovenous fistula and drug-induced peripheral arterial vasodilation. However, a predilection for the retained sodium and water to transudate into the abdominal cavity occurs with cirrhosis because of the presence of portal hypertension. The Peripheral Arterial Vasodilation Hypothesis also explains the continuum from compensated to decompensated cirrhosis to the hepatorenal syndrome.

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1,408 Citations


Journal ArticleDOI: 10.1056/NEJM199908053410603
Abstract: Background In patients with cirrhosis and spontaneous bacterial peritonitis, renal function frequently becomes impaired. This impairment is probably related to a reduction in effective arterial blood volume and is associated with a high mortality rate. We conducted a study to determine whether plasma volume expansion with intravenous albumin prevents renal impairment and reduces mortality in these patients. Methods We randomly assigned 126 patients with cirrhosis and spontaneous bacterial peritonitis to treatment with intravenous cefotaxime (63 patients) or cefotaxime and intravenous albumin (63 patients). Cefotaxime was given daily in doses that varied according to the serum creatinine level, and albumin was given at a dose of 1.5 g per kilogram of body weight at the time of diagnosis, followed by 1 g per kilogram on day 3. Renal impairment was defined as nonreversible deterioration of renal function during hospitalization. Results The infection resolved in 59 patients in the cefotaxime group (94 percent...

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Topics: Spontaneous bacterial peritonitis (62%), Hepatorenal syndrome (56%), Renal function (55%) ... read more

1,369 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA1305727
Pietro Caironi1, Gianni Tognoni2, Serge Masson2, Roberto Fumagalli3  +13 moreInstitutions (4)
Abstract: BACKGROUND Although previous studies have suggested the potential advantages of albumin administration in patients with severe sepsis, its efficacy has not been fully established. METHODS In this multicenter, open-label trial, we randomly assigned 1818 patients with severe sepsis, in 100 intensive care units (ICUs), to receive either 20% albumin and crystalloid solution or crystalloid solution alone. In the albumin group, the target serum albumin concentration was 30 g per liter or more until discharge from the ICU or 28 days after randomization. The primary outcome was death from any cause at 28 days. Secondary outcomes were death from any cause at 90 days, the number of patients with organ dysfunction and the degree of dysfunction, and length of stay in the ICU and the hospital. RESULTS During the first 7 days, patients in the albumin group, as compared with those in the crystalloid group, had a higher mean arterial pressure (P = 0.03) and lower net fluid balance (P<0.001). The total daily amount of administered fluid did not differ significantly between the two groups (P = 0.10). At 28 days, 285 of 895 patients (31.8%) in the albumin group and 288 of 900 (32.0%) in the crystalloid group had died (relative risk in the albumin group, 1.00; 95% confidence interval [CI], 0.87 to 1.14; P = 0.94). At 90 days, 365 of 888 patients (41.1%) in the albumin group and 389 of 893 (43.6%) in the crystalloid group had died (relative risk, 0.94; 95% CI, 0.85 to 1.05; P = 0.29). No significant differences in other secondary outcomes were observed between the two groups. CONCLUSIONS In patients with severe sepsis, albumin replacement in addition to crystalloids, as compared with crystalloids alone, did not improve the rate of survival at 28 and 90 days. (Funded by the Italian Medicines Agency; ALBIOS ClinicalTrials.gov number, NCT00707122.)

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Topics: Serum albumin (57%), Septic shock (54%), Intensive care (54%) ... read more

718 Citations


Journal ArticleDOI: 10.1001/JAMA.289.19.2554
21 May 2003-JAMA
Abstract: Composite outcomes, in which multiple end points are combined, are frequently used as primary outcome measures in randomized trials and are often associated with increased statistical efficiency. However, such measures may prove challenging for the interpretation of results. In this article, we examine the use of composite outcomes in major clinical trials, assess the arguments for and against them, and provide guidance on their application and reporting. To assess incidence and quality of reporting, we systematically reviewed the use of composite end points in clinical trials in Annals of Internal Medicine, BMJ, Circulation, Clinical Infectious Diseases, Journal of the American College of Cardiology, JAMA, Lancet, New England Journal of Medicine, and Stroke from 1997 through 2001 using a sensitive search strategy. We selected for review 167 original reports of randomized trials (with a total of 300 276 patients) that included a composite primary outcome that incorporated all-cause mortality. Sixty-three trials (38%) were neutral both for the primary end point and the mortality component. Sixty trials (36%) reported significant results for the primary outcome measure but not for the mortality component. Only 6 trials (4%) were significant for the mortality component but not for the primary composite outcome, whereas 19 trials (11%) were significant for both. Twenty-two trials (13%) were inadequately reported. Our review suggests that reporting of composite outcomes is generally inadequate, implying that the results apply to the individual components of the composite outcome rather than only to the overall composite. Current guidelines for the undertaking and reporting of clinical trials could be revised to reflect the common use of composite outcomes in clinical trials.

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Topics: Clinical trial (55%), Randomized controlled trial (55%), Surrogate endpoint (53%) ... read more

576 Citations


Open accessJournal ArticleDOI: 10.1002/HEP.26359
Bruce A. Runyon1Institutions (1)
01 Apr 2013-Hepatology
Abstract: Ascites is the most common of the three major complications of cirrhosis, the other complications being hepatic encephalopathy and variceal hemorrhage. Cirrhosis is the most common cause of ascites in the United States. Development of ascites may be the first evidence of the presence of cirrhosis. Obesity makes the physical examination less helpful in detecting ascites. Imaging may provide the first evidence of the presence of ascites. Patients with ascites are frequently admitted to hospitals. Effective care of these patients can reduce the frequency of these readmissions. This version of the American Association for the Study of Liver Diseases Practice Guideline is the fourth iteration of this guideline and represents a thorough update of the 2009 version. Introduction

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Topics: Cirrhosis (56%), Ascites (55%), Guideline (55%) ... read more

545 Citations