A Study of Impact of Fixed-Dose Albumin Infusion on Outcome in Patients With Cirrhosis and Infection: A Randomized Open-label Clinical Trial
Journal of clinical and experimental hepatology. 2024;14(1):101270
BACKGROUND AND AIM Antibiotics and albumin infusion constitute the standard of treatment in patients with decompensated cirrhosis who have spontaneous bacterial peritonitis (SBP). Recent studies have also shown that the use of albumin in patients with advanced liver disease who have infections other than SBP leads to the resolution of acute and chronic liver failure and prevents the development of nosocomial infections. The recommended dose of albumin for these patients is out of reach for many in resource-limited settings like India. The evidence for this recommendation is also scarce. This study aimed to assess the efficacy of a lower dose of albumin infusion in addition to antibiotics on short-term mortality and morbidity in patients with cirrhosis and infections. PATIENTS AND METHODS A prospective, open-label, randomized control study was performed. Consecutive patients with cirrhosis and infections were randomized in a 2:1 ratio into two groups: group A (116) and group B (58) patients. In addition to antibiotics and standard medical therapy, group A was given albumin in a dose of 20 g/day for five days, and group B was given the recommended dose (1.5 g/kg/body weight and 1 g/kg body weight on days one and three, respectively). The primary outcome was in-hospital mortality. Secondary outcomes were improvements in clinical and laboratory parameters. RESULTS Except for etiology, all the baseline clinical and laboratory variables in both groups were comparable. The in-hospital mortality in groups A and B was (11 [10.67%] vs. 6 [10.09%], (P = 0.965). The duration of hospitalization, 30-day mortality, improvement in shock and sensorium, and absolute improvements in serum creatinine, international normalized ratio (INR), and serum bilirubin were also comparable in both groups. CONCLUSION Low-dose albumin infusion in patients with cirrhosis and infections can have the same results as standard-dose albumin and can be used in resource-limited situations. CLINICAL TRIAL REGISTRATION NUMBER CTRI/2020/03/023794.
Midodrine versus Albumin to Prevent Paracentesis Induced Circulatory Dysfunction in Acute on Chronic Liver Failure Patients in the Outpatient Clinic-a Randomized Controlled Trial
Journal of clinical and experimental hepatology. 2023;13(4):576-585
BACKGROUND Paracentesis-induced circulatory disturbance (PICD) occurs in 12-20% of patients receiving human albumin for large-volume paracentesis, and can occur at lower than five liter paracentesis in acute-on-chronic liver failure (ACLF). Albumin infusions are associated with higher costs and more prolonged daycare admissions. The aim of the study was to determine if oral midodrine-hydrochloride can prevent PICD in these patients by increasing the mean arterial pressure (MAP). METHODS This open-labeled randomized controlled trial included ACLF patients undergoing paracentesis between 3 and 5 L, who were randomized to receive either 20% human albumin or midodrine hydrochloride 7.5 mg thrice daily for three days, 2 h before paracentesis. MAP was recorded daily. The primary outcome was the plasma renin activity (PRA) on day six, and a 50% increase from baseline was considered PICD. RESULTS 183 consecutive patients of ACLF were screened, and 50 patients were randomized to either arms. Alcohol was the most common underlying cause of cirrhosis. On day 6, PRA was non-significantly (P = 0.056) higher in the midodrine group. The absolute change of PRA between the two groups was not significant (P = 0.093). Four (16%) patients in the albumin group and five (20%) in the midodrine group developed PICD. MAP increase was not different between the albumin and midodrine arms (P = 0.851). Midodrine was found to be more cost-effective. CONCLUSIONS Three days of oral midodrine is as effective as a human-albumin infusion in preventing PICD in ACLF patients undergoing paracentesis lesser than that done in large volume paracentesis.
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.
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.
Terlipressin in combination with albumin as a therapy for hepatorenal syndrome in patients aged 65 years or older
Annals of hepatology. 2023;28(5):101126
INTRODUCTION AND OBJECTIVES Clinical data for older patients with advanced liver disease are limited. This post hoc analysis evaluated the efficacy and safety of terlipressin in patients aged ≥65 years with hepatorenal syndrome using data from 3 Phase III, randomized, placebo-controlled studies (OT-0401, REVERSE, CONFIRM). PATIENTS AND METHODS The pooled population of patients aged ≥65 years (terlipressin, n = 54; placebo, n = 36) was evaluated for hepatorenal syndrome reversal-defined as a serum creatinine level ≤1.5 mg/dL (≤132.6 μmol/L) while receiving terlipressin or placebo, without renal replacement therapy, liver transplantation, or death-and the incidence of renal replacement therapy (RRT). Safety analyses included an assessment of adverse events. RESULTS Hepatorenal syndrome reversal was almost 2-times higher in terlipressin-treated patients compared with patients who received placebo (31.5% vs 16.7%; P = 0.143). Among surviving patients, the need for RRT was significantly reduced in the terlipressin group, with an almost 3-times lower incidence of RRT versus the placebo group (Day 90: 25.0% vs 70.6%; P = 0.005). Among 23 liver-transplant-listed patients, significantly fewer patients in the terlipressin versus placebo group needed RRT by Days 30 and 60 (P = 0.027 each). Fewer patients in the terlipressin group needed RRT post-transplant (P = 0.011). More terlipressin-treated patients who were listed for and received a liver transplant were alive and RRT-free by Day 90. No new safety signals were revealed in the older subpopulation compared with previously published data. CONCLUSIONS Terlipressin therapy may lead to clinical improvements in highly vulnerable patients aged ≥65 years with hepatorenal syndrome. CLINICAL TRIAL NUMBERS OT-0401, NCT00089570; REVERSE, NCT01143246; CONFIRM, NCT02770716.
Parenclitic network mapping identifies response to targeted albumin therapy in patients hospitalized with decompensated cirrhosis
Clinical and translational gastroenterology. 2023
BACKGROUND The efficacy of targeted albumin therapy in the management of decompensatory events in cirrhosis is unclear with different reports showing conflicting results. It is possible that only certain subgroups of patients may benefit from targeted albumin administration. However, extensive conventional subgroup analyses have not yet identified these subgroups. Albumin is an important regulator of physiological networks and may interact with homeostatic mechanism differently in patients according to the integrity of their physiological network. In the present study we aimed to assess the value of network mapping in predicting response to targeted albumin therapy in patients with cirrhosis. METHOD This is a sub-study of the ATTIRE trial; a multicentre, randomized trial conducted to assess the effect of targeted albumin therapy in cirrhosis. Baseline serum bilirubin, albumin, sodium, creatinine, CRP, and white cell count (WCC), international normalised ratio, heart rate, and blood pressure of 777 patients followed up for 6 months were used for network mapping using parenclitic analysis. Parenclitic network analysis involves measuring the deviation of each individual patient from the existing network of physiological interactions in a reference population. RESULT Overall network connectivity as well as deviations along WCC-CRP axis predicted 6-month survival independent of age and model for end-stage liver disease (MELD) in the standard care arm. Patients with lower deviation along the WCC-CRP axis showed lower survival in response to targeted albumin administration over 6-month follow-up period. Likewise, patients with higher overall physiological connectivity survived significantly less than the standard care group following targeted albumin infusion. CONCLUSION The parenclitic network mapping can predict survival of patients with cirrhosis and identify patient subgroups that don't benefit from targeted albumin therapy.
Tolerance of standard dose albumin infused over 6 hrs for treatment of spontaneous bacterial peritonitis-A randomized controlled trial
Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology. 2023
BACKGROUND AND AIMS Twenty per cent albumin (1.5 g/kg at diagnosis and 1 g/kg on day three, infused over six-hour duration) is recommended particularly in high-risk spontaneous bacterial peritonitis (SBP). Whether reduced dose albumin infusion is as effective as the standard dose albumin infusion is not clear. The aim of this study was to compare standard dose albumin infusion with reduced dose albumin infusion in acute kidney injury (AKI) development or progression in patients with cirrhosis and high-risk SBP. METHODS Sixty-three patients were randomized to the standard dose albumin arm (n = 31) and reduced dose albumin arm (n = 32, 0.75 g/kg at diagnosis and 0.5 g/kg 48 h later). The albumin was infused over six-hour duration in both groups. When the patient developed respiratory distress, the albumin infusion was stopped and that dose (i.e. of day one or day three) was not restarted and no attempt was made to finish the whole dose of that day. However, the next dose was started at the pre-calculated infusion rate if there was no evidence of respiratory distress at the start of next infusion. RESULTS All 31 patients in standard dose and two (6.25%) in the reduced dose group developed symptomatic circulatory overload (p < 0.001), with infusions being stopped prematurely. The actual albumin dose received on day one was similar in both groups and only slightly higher in the standard dose group on day three. Resolution of SBP, progression of AKI to higher stage, in-hospital mortality and 28 days' mortality were similar in both groups. CONCLUSIONS For treatment of SBP, standard dose albumin infusion (1.5 g/kg at diagnosis and 1 g/kg 48 hours later) infused over six hours is not tolerated by Indian patients. The effectiveness of standard dose albumin infused over more prolonged periods, as compared to reduced dose albumin, should be evaluated in further studies. TRIAL REGISTRATION Clinical Trials.gov Identifier: NCT04273373 .
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.
Extracorporeal Albumin Dialysis in Liver Failure with MARS and SPAD: A Randomized Crossover Trial
Blood Purification. 2022;51(3):243-250
INTRODUCTION Liver failure is associated with hepatic and extrahepatic organ failure leading to a high short-term mortality rate. Extracorporeal albumin dialysis (ECAD) aims to reduce albumin-bound toxins accumulated during liver failure. ECAD detoxifies blood using albumin dialysis through an artificial semipermeable membrane with recirculation (molecular adsorbent recirculating system, MARS) or without (single-pass albumin dialysis, SPAD). METHODS We performed a randomized crossover open trial in a surgical intensive care unit. The primary outcome of the study was total bilirubin reduction during MARS and during SPAD therapies. The secondary outcomes were conjugated bilirubin and bile acid level reduction during MARS and SPAD sessions and tolerance of dialysis system devices. Inclusion criteria were adult patients presenting liver failure with factor V activity <50% associated with bilirubin ≥250 μmol/L and a complication (either hepatic encephalopathy, severe pruritus, or hepatorenal syndrome). For MARS and SPAD, the dialysis flow rate was equal to 1,000 mL/h. RESULTS Twenty crossovers have been performed. Baseline biochemical characteristics (bilirubin, ammonia, bile acids, creatinine, and urea) were not statistically different between MARS and SPAD. Both ECAD have led to a significant reduction in total bilirubin (-83 ± 67 μmol/L after MARS; -122 ± 118 μmol/L after SPAD session), conjugated bilirubin (-82 ± 61 μmol/L after MARS; -105 ± 96 μmol/L after SPAD session), and bile acid levels (-64 ± 75 μmol/L after MARS; -56 ± 56 μmol/L after SPAD session), all nondifferent comparing MARS to SPAD. CONCLUSION A simple-to-perform SPAD therapy with equal to MARS dialysate flow parameters provides the same efficacy in bilirubin and bile acid removal. However, clinically relevant endpoints have to be evaluated in randomized trials to compare MARS and SPAD therapies and to define the place of SPAD in the liver failure care program.