Use of human albumin infusion in cirrhotic patients: a systematic review and meta-analysis of randomized controlled trials
Hepatology international. 2022
BACKGROUND Human albumin infusion is effective for controlling systemic inflammation, thereby probably managing some liver cirrhosis-related complications, such as spontaneous bacterial peritonitis (SBP), hepatic encephalopathy (HE), and hepatorenal syndrome. However, its clinical benefits remain controversial. METHODS EMBASE, PubMed, and Cochrane Library databases were searched. Randomized controlled trials (RCTs) regarding use of human albumin infusion in cirrhotic patients were eligible. Mortality and incidence of liver cirrhosis-related complications were pooled. Effect of human albumin infusion on mortality was also evaluated by subgroup analyses primarily according to target population and duration of human albumin infusion treatment. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS Forty-two RCTs were finally included. Meta-analysis showed that human albumin infusion could significantly decrease the mortality of cirrhotic patients (OR = 0.81, 95% CI = 0.67-0.98, p = 0.03). Subgroup analyses showed that human albumin infusion could significantly decrease the mortality of cirrhotic patients with SBP (OR = 0.36, 95% CI = 0.20-0.64, p = 0.0005) and HE (OR = 0.43, 95% CI = 0.22-0.85, p = 0.02), but not those with ascites or non-SBP infections or undergoing large-volume paracentesis. Short-term human albumin infusion treatment could significantly decrease short-term mortality (OR = 0.67, 95% CI = 0.50-0.89, p = 0.005), but not long-term mortality. Long-term human albumin infusion treatment could not significantly decrease long-term mortality (OR = 0.72, 95% CI = 0.48-1.08, p = 0.11). In addition, human albumin infusion could significantly decrease the incidence of renal impairment (OR = 0.63, 95% CI = 0.45-0.88, p = 0.007) and ascites (OR = 0.45, 95% CI = 0.25-0.81, p = 0.007), but not infections or gastrointestinal bleeding. CONCLUSIONS Human albumin infusion may improve the outcomes of cirrhotic patients. However, its indications for different complications and infusion strategy in liver cirrhosis should be further explored.
Use of Human Albumin Administration for the Prevention and Treatment of Hyponatremia in Patients with Liver Cirrhosis: A Systematic Review and Meta-Analysis
Journal of clinical medicine. 2022;11(19)
BACKGROUND Hyponatremia is a common complication of liver cirrhosis and aggravates patients' outcomes. It may be corrected by human albumin (HA) infusion. Herein, we have conducted a systematic review and meta-analysis to evaluate the efficacy of intravenous HA administration for the prevention and treatment of hyponatremia in liver cirrhosis. METHODS Literature was searched in the PubMed, EMBASE, and Cochrane Library databases. If possible, a meta-analysis would be conducted. Incidence of hyponatremia, rate of resolution of hyponatremia, and serum sodium level were compared between cirrhotic patients who received and did not receive HA infusion. Odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated. The quality of evidence was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS Initially, 3231 papers were identified. Among them, 30 studies, including 25 randomized controlled trials (RCTs) and 5 cohort studies, were eligible. Among cirrhotic patients without hyponatremia, the HA infusion group had significantly lower incidence of hyponatremia (OR = 0.55, 95%CI = 0.38-0.80, p = 0.001) and higher serum sodium level (MD = 0.95, 95%CI = 0.47-1.43, p = 0.0001) as compared to the control group. Among cirrhotic patients with hyponatremia, the HA infusion group had a significantly higher rate of resolution of hyponatremia (OR = 1.50, 95%CI = 1.17-1.92, p = 0.001) as compared to the control group. Generally, the quality of available evidence is low. CONCLUSIONS Based on the current evidence, HA may be considered for preventing the development of hyponatremia in liver cirrhosis, especially in those undergoing LVP, and treating hyponatremia. Well-designed studies are required to clarify the effects of HA infusion on hyponatremia in liver cirrhosis.
Meta-analysis: Efficacy and safety of albumin in the prevention and treatment of complications in patients with cirrhosis
Alimentary pharmacology & therapeutics. 2022
INTRODUCTION Albumin is used in multiple situations in patients with cirrhosis, but the evidence of its benefit is not always clear. The aim was to synthesise the evidence on the efficacy and safety of albumin compared to other treatments or no active intervention in cirrhotic patients. MATERIALS AND METHODS We conducted a systematic review including randomised controlled trials (RCTs) published in MEDLINE, EMBASE and CENTRAL up to May 2022. We assessed all-cause mortality, liver transplant, cirrhosis complications of any type and serious adverse events (SAEs). Second, AEs, hospital readmission, length of hospital stay, need for paracentesis and quality of life (QoL) were evaluated. Meta-analyses with Mantel-Haenszel method and random-effects model were performed. RESULTS Fifty studies (5118 participants) were included. Albumin was associated with a reduction in mortality in cirrhotic patients with spontaneous bacterial peritonitis (SBP) (RR 0.49, 95% CI 0.32-0.75; low certainty) and hepatic encephalopathy (HE) (RR 0.53, 95% CI 0.34-0.83; low certainty) when compared to no administration of albumin, but not in other scenarios. In general, no additional benefit of albumin was found in liver transplants, SAEs or cirrhosis complications (low/very low certainty). Long-term administration (>3 months) of albumin led to a reduction in cirrhosis complications (RR 0.75, 95% CI 0.57-0.97; low certainty), hospital readmissions, length of hospital stay, need for paracentesis and improvement of QoL. CONCLUSION Albumin may reduce mortality risk in cirrhotic patients with SBP or HE. No benefit was identified in reducing liver transplants or SAEs. Long-term administration may be associated with a lower risk of cirrhosis complications and need for paracentesis.
Can albumin reduce the mortality of patients with cirrhosis and ascites? A meta-analysis of randomized controlled trials
European journal of gastroenterology & hepatology. 2022
BACKGROUND Albumin therapy in patients with decompensated liver cirrhosis has always been a controversial issue. This study aimed to investigate the efficacy and safety of albumin in reducing mortality and controlling complications in patients with liver cirrhosis and provide a reference for relevant decision-making. METHODS Databases such as PubMed, EMBASE, and Web of Science were searched to collect eligible articles published before January 2022, which were analyzed by Revman 5.3. RESULTS A total of 10 randomized controlled trials (2040 patients) were included. Based on the meta-analysis results, no significant difference in mortality was shown between the albumin administration group and the control group (HR = 1.01; 95% CI, 0.97-1.05; P = 0.62). Subgroup analysis showed that albumin administration had no significant short-term or long-term survival benefits in patients with decompensated liver cirrhosis and increased the risk of pulmonary edema adverse reactions (RR = 3.14; 95% CI, 1.48-6.65; P = 0.003). Subgroup analysis based on albumin administration time showed that short-term (HR = 0.93; 95% CI, 0.76-1.13; P = 0.47) or long-term (HR = 0.97; 95% CI: 0.87-1.08; P = 0.58) administration of albumin could not significantly reduce the mortality of patients with decompensated liver cirrhosis. In contrast, albumin administration could significantly reduce the recurrence rate of ascites (RR = 0.56; 95% CI, 0.46-0.68; P = 0.000). CONCLUSION Short-term(<1 month) or long-term (>1 month) administration of albumin can not significantly reduce the mortality of patients with decompensated liver cirrhosis, and a large amount of albumin infusion will increase the risk of pulmonary edema.
Albumin in the management of hepatic encephalopathy: a systematic review and meta-analysis
Annals of hepatology. 2021;:100541
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.
Patients with cirrhosis and hepatic encephalopathy (HE), (2 studies, n= 176).
Albumin or lactulose plus albumin (n= 86).
Saline solution or lactulose alone (n= 90).
In the meta-analysis, albumin was associated to significant lower risks of persistent HE (risk ratio - RR=0.60) and mortality (RR=0.54).
Efficacy and safety of albumin infusion for overt hepatic encephalopathy: A systematic review and meta-analysis
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2021
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.
Albumin Administration is Efficacious in the Management of Patients with Cirrhosis: A Systematic Review of the Literature
Hepatic medicine : evidence and research. 2020;12:153-172
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.
Albumin administration in patients with decompensated liver cirrhosis: a meta-analytic update
European journal of gastroenterology & hepatology. 2020
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.
Meta-analysis of individual patient data of albumin dialysis in acute-on-chronic liver failure: focus on treatment intensity
Therapeutic advances in gastroenterology. 2019;12:1756284819879565
Background: Acute-on-chronic liver failure (ACLF) is a common complication of cirrhosis characterized by single or multiple organ failures and high short-term mortality. Treatment of ACLF consists of standard medical care (SMC) and organ(s) support. Whether the efficacy of artificial liver support (ALS) depends on the severity of ACLF or on the intensity of this treatment, or both, is unclear. This study aimed to further assess these issues. Methods: We performed an individual patient data meta-analysis assessing the efficacy of Molecular Adsorbent Recirculating System (MARS) in ACLF patients enrolled in prior randomized control trials (RCTs). The meta-analysis was designed to assess the effect of patient severity (ACLF grade) and treatment intensity [low-intensity therapy (LIT), SMC alone or SMC plus 4 MARS sessions, high-intensity therapy (HIT), SMC plus > 4 MARS sessions] on mortality. Results: Three RCTs suitable for the meta-analysis (n = 285, ACLF patients = 165) were identified in a systematic review. SMC plus MARS (irrespective of the number of sessions) did not improve survival compared with SMC alone, neither in the complete population nor in the ACLF patients. Survival, however, was significantly improved in the subgroup of patients receiving HIT both in the entire cohort (10-day survival: 98.6% versus 82.8%, p = 0.001; 30-day survival: 73.9% versus 64.3%, p = 0.032) and within the ACLF patients (10-day survival: 97.8% versus 78.6%, p = 0.001; 30-day survival: 73.3% versus 58.5%, p = 0.041). Remarkably, HIT increased survival independently of ACLF grade. Independent predictors of survival were age, Model for End-Stage Liver Disease (MELD), ACLF grade, number of MARS sessions received, and intensity of MARS therapy. Conclusion: HIT with albumin dialysis may improve survival in patients with ACLF. Appropriate treatment schedules should be determined in future clinical trials.
Albumin for cirrhotic patients with extraperitoneal infections: a meta-analysis
Journal of gastroenterology and hepatology. 2019
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.