Abstract

BACKGROUND AND AIMS The efficacy and safety of albumin infusion for treatment and prevention of overt hepatic encephalopathy (OHE) among cirrhosis patients remained controversial. We performed a systematic review and meta-analysis to evaluate the benefit of albumin infusion for the treatment and prevention of OHE. METHODS We performed a systematic search of 4 electronic databases up to 31st January 2021. The primary outcome was the resolution of OHE. Secondary outcomes were inpatient mortality and albumin-associated adverse events. We assessed the pooled odds' risk, pooled mean differences, 95% confidence interval and heterogeneity using Review Manager Version 5.3. RESULTS A total of 12 studies (2,087 subjects) were identified. Among cirrhosis patients with OHE, albumin infusion was associated with a lower pooled risk of OHE (OR=0.43, 95%CI: 0.27, 0.68; I(2)=0%). Among patients without baseline OHE, albumin infusion was associated with a lower pooled risk of developing OHE (OR=0.53, 95%CI: 0.32, 0.86; I(2)=62%). Albumin infusion was associated with a lower pooled risk of inpatient mortality (OR=0.36, 95%CI: 0.21, 0.60; I(2)=0%). CONCLUSION Well-powered randomized trials are required to confirm the benefits of albumin infusion for the prevention and treatment of overt hepatic encephalopathy among decompensated cirrhosis patients.

Abstract

BACKGROUND Infection and increased systemic inflammation cause organ dysfunction and death in patients with decompensated cirrhosis. Preclinical studies provide support for an antiinflammatory role of albumin, but confirmatory large-scale clinical trials are lacking. Whether targeting a serum albumin level of 30 g per liter or greater in these patients with repeated daily infusions of 20% human albumin solution, as compared with standard care, would reduce the incidences of infection, kidney dysfunction, and death is unknown. METHODS We conducted a randomized, multicenter, open-label, parallel-group trial involving hospitalized patients with decompensated cirrhosis who had a serum albumin level of less than 30 g per liter at enrollment. Patients were randomly assigned to receive either targeted 20% human albumin solution for up to 14 days or until discharge, whichever came first, or standard care. Treatment commenced within 3 days after admission. The composite primary end point was new infection, kidney dysfunction, or death between days 3 and 15 after the initiation of treatment. RESULTS A total of 777 patients underwent randomization, and alcohol was reported to be a cause of cirrhosis in most of these patients. A median total infusion of albumin of 200 g (interquartile range, 140 to 280) per patient was administered to the targeted albumin group (increasing the albumin level to ≥30 g per liter), as compared with a median of 20 g (interquartile range, 0 to 120) per patient administered to the standard-care group (adjusted mean difference, 143 g; 95% confidence interval [CI], 127 to 158.2). The percentage of patients with a primary end-point event did not differ significantly between the targeted albumin group (113 of 380 patients [29.7%]) and the standard-care group (120 of 397 patients [30.2%]) (adjusted odds ratio, 0.98; 95% CI, 0.71 to 1.33; P = 0.87). A time-to-event analysis in which data were censored at the time of discharge or at day 15 also showed no significant between-group difference (hazard ratio, 1.04; 95% CI, 0.81 to 1.35). More severe or life-threatening serious adverse events occurred in the albumin group than in the standard-care group. CONCLUSIONS In patients hospitalized with decompensated cirrhosis, albumin infusions to increase the albumin level to a target of 30 g per liter or more was not more beneficial than the current standard care in the United Kingdom. (Funded by the Health Innovation Challenge Fund; ATTIRE EudraCT number, 2014-002300-24; ISRCT number, N14174793.).

Abstract

INTRODUCTION Patients with decompensated cirrhosis and hyponatremia have a poor prognosis. We investigated Albumin to Prevent Infection in Chronic Liver Failure trial data to determine whether targeted albumin infusions improved outcome in patients with hyponatremia at baseline. METHODS We examined the interaction between targeted albumin and standard care for the composite primary end point, stratifying by baseline sodium ≥ and <130 mmol/L. RESULTS Randomization to albumin was associated with a significant increase in sodium; however, there was no interaction between sodium category and treatment for the trial primary end point. DISCUSSION Targeted intravenous albumin infusions increased serum sodium level in hospitalized hyponatremic patients with cirrhosis, but this did not improve outcome.

Abstract

INTRODUCTION AND OBJECTIVES It has been suggested that albumin administration could alter the natural history of cirrhosis, and also, that long-term treatment with albumin might be associated with improvement in survival, control of ascites, reduction in the incidence bacterial infections, renal dysfunction, hepatic encephalopathy (HE) and hyponatremia, as well as reduction in length of hospitalization in patients with cirrhosis and ascites. The objective of the present study is to evaluate the role of albumin in the management of HE. MATERIALS AND METHODS This is a systematic review of randomized controlled trials that evaluated the use of albumin in adult patients with cirrhosis and HE. The search for eligible studies was performed in MEDLINE, EMBASE, and Cochrane CENTRAL databases until June 2020. The outcomes of interest were the complete reversal of HE and mortality. Meta-analysis was performed using the random effects model, through the Mantel-Haenszel method. RESULTS This systematic review was registered at the PROSPERO platform (CRD42020194181). The search strategy retrieved 1,118 articles. After reviewing titles and abstracts, 24 studies were considered potentially eligible, but 22 were excluded after full-text analysis. Finally, 2 studies were included. In the meta-analysis, albumin was associated to significant lower risks of persistent HE (risk ratio - RR=0.60; 95% confidence interval - CI=0.38-0.95, p=0.03) and mortality (RR=0.54; 95% CI=0.33-0.90, p=0.02). CONCLUSION Albumin administration improves HE and reduces mortality in patients with cirrhosis and HE.

Abstract

BACKGROUND Combined use of furosemide with albumin is an approved therapy to overcome diuretic resistance in treatment of ascites in decompensated chronic liver disease. Bolus dosing of diuretics has its own limitations due to pre-existing hypotension, post diuretic sodium retention and braking phenomenon. Slow albumin and furosemide Infusion has been shown to mobilize large ascites with improved diuresis and hemodynamic stability in decompensated chronic liver disease. This study was undertaken to compare efficacy and safety of infusion therapy vs bolus therapy in term the management of refractory ascites. METHODS Decompensated chronic liver disease patients with refractory ascites were randomly assigned into two groups of 15 each - Bolus therapy (intravenous albumin and furosemide as boluses) and Infusion therapy (furosemide infusion at 2mg/hour and albumin at 2g/hour for three days). Diuresis, natriuresis, change in abdominal girth and body weight, and hemodynamic stability (change in SBP) were compared between the two groups. RESULTS Infusion therapy, as compared to bolus therapy, showed a significantly better diuresis (mean urinary output increment 483ml vs 243ml, p <0.001), natriuresis (mean urinary sodium excretion increment 35.2 mEq/L vs 16.6 mEq/L, p = 0.004),decrease in abdominal circumference (6.1cm vs 3.0cm, p<0.001) and decrease in body weight (5.53 Kg vs 2.86 Kg, p < 0.001). The complications of renal impairment were also lower in the Infusion group. CONCLUSION Infusion of furosemide and albumin is a potential safer and effective therapeutic option in the management of refractory ascites with better natriuresis, higher urine output, and higher decrement in abdominal circumference and body weight, and lesser side effects.

Abstract

The use of albumin in patients with cirrhosis has been extensively discussed over recent years. Current treatment approaches depend on targeting related complications, aiming to treat and/or prevent circulatory dysfunction, bacterial infections and multi-organ failure. Albumin has been shown to prolong survival and reduce complications in patients with cirrhosis. This review aims to ascertain whether the use of albumin is justified in patients with cirrhosis. A systematic review of randomized controlled trials (RCTs) and meta-analyses evaluating albumin use in patients with cirrhosis published between 1985 and February 2020 was conducted; the quality and risk of bias of the included studies were assessed. In total, 45 RCTs and 10 meta-analyses were included. Based on the included evidence, albumin is superior at preventing and controlling the incidence of cirrhosis complications vs other plasma expanders. Recent studies reported that long-term albumin administration to patients with decompensated cirrhosis improves survival with a 38% reduction in the mortality hazard ratio compared with standard medical treatment alone. Albumin infusions are justified for routine use in patients with cirrhosis, and the use of albumin either alone or in combination with other treatments leads to clinical benefits. Long-term administration of albumin should be considered in some patients.

Abstract

End-stage liver disease and its related complications exert a huge disease burden and reduce the survival rates of many patients. Albumin administration for patients with decompensated liver cirrhosis has been a controversial topic of discussion. The aim of this study is to investigate whether albumin reduces the mortality and complications of liver cirrhosis compared to standard medical therapy (SMT) alone. Clinical trials in which albumin administration was compared to SMT in patients with liver cirrhosis were included in this meta-analysis. The primary outcome of this study was to evaluate the effect on reducing all-cause mortality. Ascites control, renal failure and hepatic encephalopathy were evaluated as secondary outcomes. Nine clinical trials with 1231 patients were recruited and analyzed using the quality effect model. Mortality rate was significantly reduced in the albumin group [relative risk (RR) 0.73, 95% confidence interval (CI) 0.56-0.96]. Heterogeneity was mild across all studies (I 23.3%). Studies reporting long-term albumin (LTA) administration were found to have a significant decrease in mortality (RR 0.57, 95% CI 0.44-0.73). However, studies reporting short-term albumin administration were found to have no effect on mortality (RR 0.90, 95% CI 0.56-1.45). Furthermore, there was a significant decrease in the incidence of all secondary outcomes. This meta-analysis provides evidence that LTA administration is significantly effective in reducing the mortality of liver cirrhosis compared to SMT. Albumin administration was also shown to reduce the occurrence of ascites, renal failure and hepatic encephalopathy as complications of liver cirrhosis.

Abstract

BACKGROUND & AIMS We performed a randomized trial to determine whether albumin should be administered to patients with infections unrelated to spontaneous bacterial peritonitis (SBP). METHODS We performed a multicenter, open-label trial in which 118 patients with cirrhosis, non-SBP infections, and additional risk factors for poor outcome were randomly assigned to receive antibiotics plus albumin (study group; n=61) or antibiotics alone (control group; n=57). The primary outcome was in-hospital mortality; secondary outcomes were effect of albumin on disease course. RESULTS There were no significant differences at baseline between groups in results from standard laboratory tests, serum markers of inflammation, circulatory dysfunction, or liver severity scores. However, the combined prevalence of acute on chronic liver failure (ACLF) and kidney dysfunction was significantly higher in the study group (44.3% vs 24.6% in the control group; P=.02), indicating greater baseline overall severity. There was no significant difference in the primary outcome between groups (13.1% in the study group vs 10.5% in the control group; P=.66). Circulatory and renal functions improved in only the study group. A significantly higher proportion of patients in the study group had resolution of ACLF (82.3% vs 33.3% in the control group; P=.03). A significantly lower proportion of patients in the study group developed nosocomial infections (6.6% vs 24.6% in the control group; P=.007). CONCLUSIONS In a randomized trial of patients with advanced cirrhosis and non-SBP infections, in-hospital mortality was similar between those who received albumin plus antibiotics vs those who received only antibiotics (controls). However, patients given albumin were sicker at baseline and, during the follow-up period, a higher proportion had ACLF resolution and a lower proportion had nosocomial infections. ClinicalTrials.gov no: NCT02034279.

Abstract

BACKGROUND AND AIM Bacterial infections are among the main causes of death in patients with cirrhosis. While there are unquestionable benefits of using albumin in patients with spontaneous bacterial peritonitis, the benefits of albumin are controversial for those with extraperitoneal infections. The aim was to compare the use of albumin associated to antibiotics and antibiotics alone in cirrhotic patients with extraperitoneal infections. METHODS A systematic review was performed using MEDLINE and EMBASE databases. Randomized controlled trials comparing albumin associated to antibiotics and antibiotics alone in cirrhotic patients with extraperitoneal infections were considered eligible, as long as at least one of the following outcomes was evaluated: mortality; renal dysfunction. Meta-analysis was performed using the random effects model, through the Mantel-Haenszel method. The study protocol was registered at PROSPERO platform (CRD42018107191). RESULTS The literature search yielded 812 references. Three randomized controlled trials fulfilled the selection criteria and were included in this meta-analysis. There was no evidence of significant difference between the groups regarding mortality in 30 days (risk ratio - RR = 1.62, 95% confidence interval - CI: 0.92 - 2.84, p = 0.09, I(2) = 0%) or in 90 days (RR = 1.27, 95%CI: 0.89 - 1.83, p = 0.19, I(2) = 0%). Regarding renal dysfunction, there was also no evidence of significant difference between the groups (RR = 0.55, 95%CI: 0.25 - 1.19, p = 0.13, I(2) = 0%). CONCLUSION There is no evidence of significant benefits of using albumin for cirrhotic patients with extraperitoneal infections regarding mortality or renal dysfunction.

Abstract

Paracentesis-induced circulatory dysfunction (PICD) is a serious complication of large-volume (>5 L) paracentesis in cirrhosis and is reduced with albumin infusion. There is a lack of data on PICD in acute-on-chronic liver failure (ACLF). Because ACLF patients have greater hemodynamic derangements than patients with decompensated cirrhosis, we investigated whether PICD could develop with modest-volume paracentesis (MVP) and the role of albumin infusion. A total of 80 ACLF patients undergoing <5 L paracentesis were randomized to receive albumin (8-10 g/L of ascitic fluid; n = 40) or no albumin (n = 40) and were serially followed to detect PICD. Baseline characteristics were comparable between groups, including volume of ascitic tap (4.16 +/- 0.23 vs. 4.14 +/- 0.27 L; P = 0.72) and plasma renin activity (PRA) (20.5 +/- 7.03 vs. 23.2 +/- 8.24 ng/mL/hour; P = 0.12). PICD was more frequent in the no-albumin group than the albumin group (70% vs. 30%; P = 0.001), with higher incidence of hepatic encephalopathy (50% vs. 27.5%; P = 0.04), hyponatremia (67.5% vs. 22.5%; P < 0.001), acute kidney injury (62.5% vs. 30%; P = 0.001), and in-house mortality (62.5% vs. 27.5%; P = 0.003). PRA of 25.15 ng/mL at day 3 had sensitivity and specificity of 71% and 68% for development of PICD at day 6. Albumin infusion decreased the incidence of PICD at day six (odds ratio, 0.068; 95% confidence interval, 0.011-0.43; P = 0.005). Conclusion: PICD is common and develops even with MVP in ACLF patients. Albumin infusion decreases the incidence of PICD and mortality in ACLF patients.