Human Albumin Infusion for the Management of Liver Cirrhosis and Its Complications: An Overview of Major Findings from Meta-analyses
Advances in therapy. 2023
INTRODUCTION The role of human albumin (HA) infusion in cirrhotic patients has been increasingly recognized. This paper aims to summarize the evidence from meta-analyses regarding HA infusion for the management of cirrhosis and its complications. METHODS A systematic search in the PubMed, EMBASE, and Cochrane library databases, and in reference lists was conducted. All relevant meta-analyses were identified and their findings were reviewed. The Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) checklist was used to evaluate the methodological quality and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system to assess the quality of evidence for significant outcomes. RESULTS Among 300 papers initially identified, 18 meta-analyses have been included. Short- and long-term HA infusion at high doses decreased the mortality of patients with decompensated cirrhosis. In cirrhotic patients with ascites, long-term HA infusion reduced the recurrence of ascites, but not mortality. In cirrhotic patients undergoing large-volume paracentesis (LVP), HA infusion reduced the incidence of post-paracentesis circulatory dysfunction and hyponatremia, but not mortality or renal impairment. In cirrhotic patients with overt hepatic encephalopathy (HE), HA infusion improved the severity of overt HE, but not overall mortality. In cirrhotic patients with spontaneous bacterial peritonitis (SBP), but not those with non-SBP infections, HA infusion reduced the mortality and renal impairment. In cirrhotic patients with type-1 hepatorenal syndrome (HRS), an increment of 100 g in cumulative HA dose increased 1.15-fold survival, but not HRS reversal. In these meta-analyses, the quality of methodology was low or critically low, and that of the evidence was from very low to moderate. CONCLUSIONS Based on the limited evidence from these meta-analyses, HA infusion appears to be beneficial in cirrhotic patients with ascites, overt HE, and SBP and in those undergoing LVP, but not in those with non-SBP infections.
Efficacy and Safety of Prothrombin Complex Concentrates in Liver Transplantation: Evidence from Observational Studies
Journal of clinical medicine. 2023;12(11)
The risk/benefit ratio of using prothrombin complex concentrates (PCCs) to correct coagulation defects in patients with end-stage liver disease is still unclear. The primary aim of this review was to assess the clinical effectiveness of PCCs in reducing transfusion requirements in patients undergoing liver transplantation (LT). This systematic review of non-randomized clinical trials was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was previously registered (PROSPEROCRD42022357627). The primary outcome was the mean number of transfused units for each blood product, including red blood cells (RBCs), fresh frozen plasma, platelets, and cryoprecipitate. Secondary outcomes included the incidence of arterial thrombosis, acute kidney injury, and haemodialysis, and hospital and intensive care unit length of stay. There were 638 patients from 4 studies considered for meta-analysis. PCC use did not affect blood product transfusions. Sensitivity analysis, including only four-factor PCC, showed a significant reduction of RBC effect size (MD: 2.06; 95%CI: 1.27-2.84) with no true heterogeneity. No significant differences in secondary outcomes were detected. Preliminary evidence indicated a lack of PCC efficacy in reducing blood product transfusions during LT, but further investigation is needed. In particular, future studies should be tailored to establish if LT patients will likely benefit from four-factor PCC therapy.
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.
Efficacy of Intravenous Albumin for Spontaneous Bacterial Peritonitis Infection Among Patients With Cirrhosis: A Meta-Analysis of Randomized Control Trials
Albumin is an important component in the standard therapeutic approach to spontaneous bacterial peritonitis (SBP). This meta-analysis aimed to determine the impact of intravenous human albumin in patients with cirrhosis and SBP. This study was conducted according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two reviewers independently searched relevant studies using electronic databases including PubMed, Embase and Cochrane Library from the date of database inception to October 2022. The outcomes assessed in the current meta-analysis include 30-day mortality, renal impairment, changes in serum creatinine levels (mg/dl) and resolution of bacterial infection. It was found that the risk of all-cause mortality and renal impairment was significantly lower in patients receiving albumin compared to the control group. However, no significant difference was reported between the two groups in relation to changes in mean creatinine levels and resolution of infection.
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.
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.
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.
Prophylactic fresh frozen plasma versus prothrombin complex concentrate for preprocedural management of the coagulopathy of liver disease: A systematic review
Research and practice in thrombosis and haemostasis. 2022;6(4):e12724
BACKGROUND The optimal prophylactic preprocedural management of patients with coagulopathy due to liver disease is not known. OBJECTIVES Our objective was to compare the efficacy and safety of fresh frozen plasma (FFP) with prothrombin complex concentrate (PCC) in the preprocedural management of patients with coagulopathy of liver disease. METHODS We conducted a systematic review to examine published evidence regarding treatment with FFP or PCC in adults with coagulopathy of liver disease undergoing an invasive procedure. Direct comparisons and single-arm studies were eligible. Efficacy outcomes included major bleeding, mortality, and correction of prothrombin time (PT) and/or international normalized ratio (INR). Safety outcomes included thrombosis and transfusion-related complications. RESULTS A total of 95 articles were identified for full-text review. Nine studies were eligible and included in the review. No randomized trials comparing FFP versus PCC were identified. Only two studies directly compared FFP versus PCC. In these studies, PCC appeared to result in higher rates of correction of PT/INR, but bleeding outcomes were not different. In the single-arm studies, bleeding events appeared low overall. Volume overload was the most common recorded adverse event in patients receiving FFP. Thromboembolic events occurred rarely, but exclusively in the PCC group. Due to heterogeneity in study definitions and bias, meta-analysis was not possible. Our study found no evidence to favor a specific product over another. CONCLUSIONS Insufficient data exist on the effects of FFP versus PCC administration before invasive procedures in patients with coagulopathy of liver disease to make conclusions with respect to relative efficacy or safety.
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.